Number Of CD8 Research Articles

Analysis of immunopathogenesis of psoriasis in the dynamics of treatment

Оbjective — to analyze the parameters of the immune system of the organism in patients with psoriasis before and after treatment. Materials and methods. The parameters of cellular immunity in an organism estimated after the change of relative and absolute amount of T- (CD3+) and B- (CD19+) of lymphocytes and subpopulations (CD4+, CD8+, CD16+, CD25+, CD71+, CD30+, CD95+). To identify of surface structures of lymphocytes the method of direct immune fluorescence was used where fluorescent label was attached to anti-CD of mononuclear antibodies of series Leu of the firm «Becton Dikinson» (USA). Calculations were conducted on the laser instantaneous cytofluorometer of the firm «Baston» (USA). Results and discussions. The most positive influence on the parameters of the cellular link of the immune system of the organism was found in patients with psoriasis who received immunobiological therapy with the medication etanercept in combination with narrowband (311 nm) phototherapy. After treatment in patients of this group, due to a significant decrease in the production of TNF and its serum concentration, the pro-inflammatory changes in the cellular link of the immune system decreased, the number of lymphocytes with the an early activation marker, which initiated a further cytokine cascade of development and prolongation of inflammation decreased significantly. In addition, the established reduction in the number of CD30+ lymphocytes is an indirect factor indicating the switching of the Tx2 response (autoimmune manifestations) to Tx1, and hence the achievement of the clinical and immunological remission of the psoriatic process. It is extremely important for the functioning of the immune system the decrease in the content of activated lymphocytes that express the Fas-receptor as due to the increased lymphocyte apoptosis, namely, T-cytotoxic lymphocytes, and autoimmune and proliferative changes took place inherent in the exacerbation of the psoriatic process. Conclusions. It was established that all our schemes of psoriasis treatment have immunorehabiting properties but their degree of severity was different. The most effective treatment scheme is the combined use of etanercept and UVB therapy, thus proliferative and inflammatory changes in the skin reduced, antigenic loading decreased, the level of CICs, autosensibilization and autoimmune disorders also decreased.

The relationship between serum interleukin-1β and circulating CD16+ neutrophils for assessing progression-free time in advanced ovarian cancer

BACKGROUND: Ovarian cancer is the most aggressive gynecological tumor with high mortality. The ambivalent, both helper and suppressive effects of neutrophils on the cells of innate and adaptive immunity determines their important immunoregulatory role in the development of malignant tumors. AIM: Evaluation of the effect of serum interleukin-1β and circulating neutrophils CD16+ on progression-free time in advanced ovarian cancer. MATERIAL AND METHODS: In 42 primary patients with serous ovarian adenocarcinoma (median age 54 years) with ascites and 15 patients with benign ovarian tumors (median age 60 years) admitted for examination and treatment to the Regional Clinical Oncology Dispensary before receiving neoadjuvant antitumor treatment (2015–2020), the level of interleukin-1β in the blood serum was determined using enzyme immunoassay, and the number of CD16+ neutrophils was determined by fluorescence microscopy using monoclonal antibodies. Statistical processing was performed using Statistica 13 and Jamovi 2.4.14 programs. Progression-free time analysis of patients was performed using the Cox and Kaplan–Meier regression methods. RESULTS: It was found that the number of circulating CD16+ neutrophils in advanced ovarian cancer with ascites was lower than in benign ovarian tumors [48.0; 95% confidence interval (CI) 46.59–48.12 versus 50.0; 95% CI 48.51–49.76; p=0.017]. At the same time, the level of interleukin-1β in the blood serum in advanced ovarian cancer with ascites was higher than in benign ovarian tumors [2.52 (95% CI 2.50–3.37) versus 1.26 (95% CI 0.97–1.55) (p=0.0001)]. In multivariate Cox analysis in patients with ascites (odds ratio 4.334; 95% CI 1.83–10.23; p=0.001), both the CD16+ neutrophil count (odds ratio 0.73; 95% CI 0.62–0.86; p=0.0001) and serum interleukin-1β levels (odds ratio 1.90; 95% CI 1.41–2.57; p=0.0001) had prognostic significance for assessing progression-free time. CONCLUSION: The number of circulating CD16+ neutrophils and serum interleukin-1β levels simultaneously affect progression-free time in advanced ovarian cancer.

Efficacy and Safety of Rituximab Treatment for Anti-N-Methyl-d-Aspartate Receptor Encephalitis Without Tumor in Children

BackgroundTo evaluate the efficacy and safety of rituximab treatment for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis without tumor in children. MethodsEighteen pediatric patients with NMDAR encephalitis treated with rituximab after failure of intravenous immunoglobulin (IVIG) and methylprednisolone treatment were analyzed retrospectively in terms of their medical history, clinical features, laboratory examination results, and treatments. The modified Rankin scale (mRS) score, peripheral blood CD19+ B cells, recurrence, and adverse events were used to evaluate the efficacy and safety of rituximab. ResultsThe patients were treated with rituximab 3.2 ± 1.0 days after the end of IVIG and methylprednisolone treatment. After initial rituximab treatment for four weeks, the mRS score and number of CD19+ B cells in all patients were significantly lower than those before treatment (P < 0.05). At the last follow-up (44.1 months, 17.7 S.D.), all patients had recovered well (mRS ≤2), 14 patients (77.8%) recovered completely (mRS = 0), three patients had recurrent seizures, and one patient had mental and language impairment. Two patients had transient mild adverse events during infusion, and none of the other patients experienced severe adverse events during hospitalization or follow-up. ConclusionsRituximab appears safe and may be effective for the treatment of anti-NMDAR encephalitis without tumor in children refractory to first-line agents.

HDAC6 Deletion Decreases Pristane-induced Inflammation.

Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy

PurposeAchieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR.MethodsThis was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system.ResultsHeterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and β-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001).ConclusionsNCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study

BackgroundThe oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF).MethodsThis descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανβ-3 and HOXA10 in endometrium were collected.ResultsThirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27–40 years) completed the research. The median number of embryo transfer cycles was three (range 3–8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0–13.5) to 0.65 (range 0–6), P = 0.035; additionally, the H-score of expression of ανβ-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%).ConclusionsThese results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανβ-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

Identifying the role of antigen-specific resident memory CD4 T cells in maintaining disease during Experimental Autoimmune Encephalomyelitis a murine model of Multiple Sclerosis.

Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) driven by antigen-specific CD4+ T cell mediated destruction of the myelin sheath. Most T cells circulate between lymphoid organs and peripheral tissues, but a fraction can establish tissue residence and do not recirculate. Growing evidence suggests resident T cells exist in the CNS of MS patients, however, their contribution to disease progression and whether they can cause relapses independently of peripheral T cells is unclear. Current disease modifying therapies for MS patients are not curative and none target CNS resident T cells. Using a murine model of MS, Experimental autoimmune encephalomyelitis (EAE), we investigated whether resident T cells form in the CNS of diseased mice and their contribution to disease pathogenesis. Our data show that antigen-specific CNS resident T cells can be detected during EAE by intravital antibody staining and CD69 expression. Following depletion of circulating CD4+ T cells, CNS resident CD69+ CD4+ T cells maintained their numbers, while the number of CD69- T cells in the CNS was significantly depleted. These CNS resident T cells can drive severe disease in the absence of circulating CD4+ T cells and showed memory-like properties including high proliferative capacity and increased cytokine polyfunctionality compared to early effector T cells. Therefore, disruption of resident T cell function in MS patients could represent a novel target for MS therapies.

The Relationship between Serum Zonulin and Innate Immunity in Patients with Inflammatory Bowel Disease

The aim of the study was to investigate the relationship between the serum zonulin and the cellular immunity in patients with ulcerative colitis (UC) and Crohn’s disease (CD). The study included 97 patients, 13 (13.4%) patients with CD and 84 (86.6%) patients with UC. The concentration of zonulin in the serum was studied using the ELISA kits. The investigation of the circulated leukocyte subpopulation was carried out through flow cytometry. The functional activity of the circulating neutrophils was studied using the absorption capacity of the monodisperse polystyrene latex particles and indicators of oxygen-dependent metabolism in the nitroblue tetrazolium test. The serum zonulin concentration in CD patients was significantly higher compared with UC patients (p = 0.003). The zonulin concentration directly correlated with the functional activity of the circulating neutrophils. Patients with a zonulin concentration &gt; 472.4 pg/mL had a significantly higher number of band neutrophils (p = 0.0104), CD3+CD8+ cells (p = 0.0212), NK cells (p = 0.0161), and lower–CD19+ cells (p = 0.0034). Among the IBD patients, zonulin was associated with IBD severity. An increase in the serum concentration of zonulin was associated with an increase in the functional activity of circulating neutrophils and an increase in the number of CD3+CD8+ cells, NK cells, and a decrease in the number of CD19+ cells.

LncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

Endometrial NK cells in repeated implantation failure – quantity and functional markers

BACKGROUND: Alteration in the composition and function of endometrial immune cells, in particular NK cells, are associated with implantation and placentation pathology, which is considered as one of the causes of reproductive losses. However, data regarding abnormalities in the number and activity of NK cells in repeated implantation failures, including depending on the type of infertility, remain ambiguous.&#x0D; AIM: The aim of this study was to evaluate the number of CD56+ and CD16+ cells and the area of expression of CD107a and NKG2D markers in the endometrium of patients with repeated implantation failure (RIF).&#x0D; MATERIALS AND METHODS: This prospective comparative study included patients with RIF (main group I, n = 47), who were divided into two subgroups: Ia, patients with primary infertility (n = 29); Ib, patients with secondary infertility (n = 18). Comparison group II included patients with a history of effective ART programs (n = 17). Control group III included healthy fertile women without a history of reproductive loss (n = 12). Endometrial biopsies were obtained on days 19–23 of the menstrual cycle. The expression of CD56+, CD16+, CD107a and NKG2D was assessed by immunohistochemistry.&#x0D; RESULTS: In the endometrium of patients in groups I and II, as compared to the control group, the number of CD56+ cells was significantly increased (p 0.001). In patients of subgroup Ia, when compared to the control group, we verified an increase in the number of CD16+ cells (p 0.05) and a decrease in the expression of CD107a (p 0.05). In patients in groups I and II, a negative correlation was revealed between the number of CD56+ and CD16+ cells and the number of pregnancies in history (rs = –0.30 and rs = –0.34, p 0.05), while a positive correlation was found between the expressions of CD56+ and CD107a (rs = 0.66 and rs = 0.75, p 0.05). In patients in group II, a positive correlation was revealed between the expressions of CD16+ and CD107a (rs = 0.75, p 0.05). In the endometrial stroma, CD107a expression increased significantly in patients in group I (p 0.05), while NKG2D expression increased in groups II and III (p 0.01, p 0.05) from the early to the middle stage of the secretion phase. In patients of group II, a positive correlation was established between the expressions of CD56+ and NKG2D (rs = 0.68, p 0.05).&#x0D; CONCLUSIONS: In the endometrium of patients with primary infertility and RIF, the number of CD56+ and CD16+ cells is increased with a decrease in the expression of their activation marker CD107a, which may be a potential mechanism for impaired implantation. Further studies of the immune profile of the endometrium may help to personalize diagnostic and therapeutic approaches to management of patients with RIF and to increase the chances of pregnancy in ART programs.

Broadening the horizon: potential applications of CAR-T cells beyond current indications.

Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström's macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.

Development of [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A for PET imaging to noninvasively assess cancer reactive T cell infiltration: Fab-based CD103 immunoPET

BackgroundCD103 is an integrin specifically expressed on the surface of cancer-reactive T cells. The number of CD103+ T cells significantly increases during successful immunotherapy and might therefore be an attractive biomarker for noninvasive PET imaging of immunotherapy response. Since the long half-life of antibodies preclude repeat imaging of CD103+ T cell dynamics early in therapy, we therefore here explored PET imaging with CD103 Fab fragments radiolabeled with a longer (89Zr) and shorter-lived radionuclide (68Ga).MethodsAntihuman CD103 Fab fragment Fab01A was radiolabeled with 89Zr or 68Ga, generating [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A, respectively. In vivo evaluation of these tracers was performed in male nude mice (BALB/cOlaHsd-Foxn1nu) with established CD103-expressing CHO (CHO.CD103) or CHO-wildtype (CHO.K1) xenografts, followed by serial PET imaging and ex vivo bio-distribution.Results[89Zr]Zr-hCD103.Fab01A showed high tracer uptake in CD103+ xenografts as early as 3 h post-injection. However, the background signal remained high in the 3- and 6-h scans. The background was relatively low at 24 h after injection with sufficient tumor uptake. [68Ga]Ga-hCD103.Fab01Ashowed acceptable uptake and signal-to-noise ratio in CD103+ xenografts after 3 h, which decreased at subsequent time points.Conclusion[89Zr]Zr-hCD103.Fab01A demonstrated a relatively low background and high xenograft uptake in scans as early as 6 h post-injection and could be explored for repeat imaging during immunotherapy in clinical trials. 18F or 64Cu could be explored as alternative to 68Ga in optimizing half-life and radiation burden of the tracer.

Non-Interventional Observational Analysis of the Clinical Outcomes with IO-FIVE (Immune-Oncology Fast In Vivo Efficacy Test) in Lymphoma Patients

Background: Lymphoma is a malignant lymphatic system tumor with a significant global incidence. The treatment of lymphoma involves various approaches, including chemotherapy, immunotherapy, and immune checkpoint inhibitor therapy, which are considered promising avenues for exploration. Currently, Patient-Derived Xenograft model (PDX model), as the classical mouse xenograft tumor model that best represents the genetic information characteristics of human tumors, can be used to predict the therapeutic effect, and develop individualized treatment for patients. However, due to the lack of immune cells in the model, there is insufficient evidence at a satisfactory level to support functional testing of immunotherapeutic agents which are now widely available. We explored the drug efficacy consistency of a functional testing technology called Immuno-oncology Fast in Vivo Efficacy (IO-FIVE), which possesses the ability to evaluate immune drug efficacy, in patients with lymphoma. Methods: This study was a non-interventional observational research. The patient's sample was collected for IO-FIVE testing. However, the patient's clinical treatment was in accordance with clinical guideline and experience, without reference to the IO-FIVE results. Post hoc analyses were designed to evaluate the consistency of IO-FIVE with clinical outcomes in patients with lymphoma. The experimental procedure of IO-FIVE is as follows: Fresh tumor samples and peripheral blood from clinical patients are obtained and enzymatically digested into single-cell suspensions. Tumor cells and immune cells are then mixed in the predetermined ratio and loaded into the dedicated IO-FIVE device. The device is subsequently implanted subcutaneously in mice, followed by a systemic drug administration for 10 days. Finally, the device is retrieved, and its relative fluorescence intensity is measured to determine the cytotoxic effect of the drug on tumor cells. Results: A total of 12 patients underwent treatment, with drug sensitivity testing conducted on the clinical drug regimens of 8 patients using IO-FIVE. These 8 patients included 3 cases of T-cell lymphoma and 5 cases of B-cell lymphoma. The clinical outcomes and prognosis of 4 (50%) patients were consistent with IO-FIVE results (Patient ID: 1, 7, 8 and 9), with 2 cases demonstrating positive consistency and 2 cases showing negative consistency. The tested regimens included chemotherapy drugs and immunotherapy drugs. It is worth noting that among the samples with inconsistent results (ID: 3, 6, 11 and 12), we observed that patient 3 benefited from the clinical use of R-CHOP combined with Zanubrutinib in controlling cancer. Patient 6 initially responded well to the R-CHOP regimen clinically but experienced rapid disease progression due to cachexia. Furthermore, through flow cytometric analysis, we observed a significant reduction in the number of CD20 + B cells during the administration cycles of R-CHOP, suggesting the involvement of CD20 + B cells in tumor cytotoxicity. Conclusion: The IO-FIVE drug sensitivity testing technology has demonstrated a certain level of clinical consistency. However, its evaluation is limited by the insufficient number of samples and lack of follow-up clinical data, which prevents a complete alignment between IO-FIVE and clinical data. As a result, determining the correlation between IO-FIVE results and clinical outcomes accurately remains challenging. To address this, prospective randomized controlled trials (RCTs) are needed to match IO-FIVE results with patient clinical outcomes, providing new evidence for assessing the clinical consistency of IO-FIVE.

Usefulness of Biopsy Specimens for Evaluating CD103+ Tumor-resident Memory T Cells in Esophageal Cancer.

CD103+ tissue-resident memory T cells (TRM) in tumor sites are associated with a favorable prognosis and predict the effectiveness of immune checkpoint inhibitors. The detection of CD103+ TRM infiltration in biopsy samples could be beneficial for patients without surgical indications. However, the usefulness of TRM detection in biopsy tissue and the difference in TRM status between biopsy and surgical specimens' post-neoadjuvant chemotherapy have not been elucidated. In the present study, we aimed to elucidate whether we can detect TRM in biopsy specimens and the impact of chemotherapy on TRM infiltration. Tissue sections were obtained from 46 patients with esophageal cancer who received neoadjuvant chemotherapy and underwent radical esophagectomy in 2017. Immunohistochemistry was performed using an anti-CD103 antibody for biopsy and surgical specimens. We examined the relationship between CD103 expression, clinicopathological features, and prognosis for each patient. TRM infiltration was detected in the biopsy specimens. CD103 expression in biopsy specimens correlated with that in surgical specimens. Although there was no statistical significance in clinicopathological findings between CD103high and CD103low, patients with CD103high biopsy specimens exhibited favorable prognosis. The number of CD103+ cells was increased by chemotherapy: though with no survival benefit. Regardless of surgical indication, we were able to determine the TRM status even in biopsy specimens. CD103 evaluation at biopsy may be more useful and practical than evaluation in surgical specimens, enabling prediction of prognosis and response to immune therapy.

The Association of NKp46-Positive uNK Cells With a Higher Risk of Recurrent Miscarriage and IVF Failure

Background: Uterine natural killer (uNK) cells have a significant impact on pregnancy and related complications. Given the importance of receptors in the activity of uNK cells, the present study aimed to determine the number of uNK cells and NKp46 (one of the most important NK cell-activating receptors) expression in the endometrium of women with recurrent miscarriage (RM) or a history of in vitro fertilization (IVF) failure. Materials and Methods: This case-control study was performed on 48 participants, including 16 healthy controls, 27 cases with RM, and 5 cases with repeated implantation failure (RIF) during the mid-luteal phase according to a standardized diagnostic protocol. All participants were assessed using transvaginal ultrasound to determine embryo survival rate and confirm gestational age. Endometrial specimens were collected and subjected to immunohistochemistry (IHC) staining using an anti-human NKp46 antibody expressed by uNK cells. Results: A significantly higher number of cells positive for NKp46 was obtained among two groups of cases versus healthy subjects (patients: 1.46±0.78, controls: 0.82±62, P=0.006), and the number of CD56+cells was significantly higher in patients than in controls (patients: 18.14±7.14, controls: 11.71±6.17, P=0.003). Additionally, there was not a significant difference in the frequency ratio of NKp46+NK cell subset to CD56+uNK cells between the patients (P=0.59) and control healthy group. Conclusion: The increase in the number of uterine NK cells and their cytotoxic activity during implantation and early pregnancy, possibly resulting from an excessive expression of inflammatory cytokines, confirms a significant association between uNK cell activity and a higher risk of RM and RIF. Therefore, immunomodulatory treatments may benefit these patients.

Immunophenotypic Characterization of Citrate-Containing A Concentrates in Maintenance Hemodialysis: A Pre-Post Study.

Due to chronic inflammation, maintenance hemodialysis (MHD) patients continue to show excess mortality. Acetate-free citrate-buffered A concentrates could be a way to improve the biocompatibility of the procedure, reduce chronic inflammation, and thus in the long term improve the prognosis of patients. Using a pre-post design (3 months of acetate followed by 3 months of citrate-acidified A concentrates in standard bicarbonate-based dialysate hemodialysis, CiaHD) and linear mixed model analysis in 61 stable HD patients, we assessed the impact of CiaHD on counts and phenotypes of peripheral T cells and monocytes by flow cytometry. Switching to CiaHD left C-reactive protein (CRP) levels and leucocyte counts unaffected. However, CiaHD increased lymphocyte counts ex vivo. Furthermore, we found a decrease in total CD3+CD4+CD69+ ((109/L), mean ± SD: acetate, 0.04 ± 1.0 versus citrate, 0.02 ± 0.01; P = 0.02) activated cells, while the number of CD28+ T cells remained stable. No differences were noted regarding T-cell exhaustion marker expression, CD14+CD16+ monocyte counts, and PMN-MDSCs. Compared with acetate, CiaHD has a minor impact on lymphocyte counts and CD4+T-cell activation, which was independent of systemic CRP and ionized magnesium, calcium levels, and other dialysis prescription modalities.

Curcumin ameliorates traumatic brain injury via C1ql3-mediated microglia M2 polarization

PurposeCurcumin can regulate the polarization of microglia and alleviate traumatic brain injury (TBI). However, its detailed action mechanism on downregulating Complement 1q-like-3 protein (C1ql3) in TBI is less reported. The purpose of this study is to explore the role and mechanism of curcumin-regulated C1ql3 in TBI. MethodGSE23639 dataset was used to acquire gene data for microglia. C57BL/6 J wild-type (WT) mice were subjected to establish a controlled cortical impact model of TBI. The effects of curcumin (200 mg/kg) on the brain injury, inflammatory cytokine levels, microglia polarization, and C1ql3 protein expression in mice and BV-2 cells were detected by H&E staining, qRT-PCR, immunofluorescence, and Western blot, respectively. The effects of curcumin (5, 10, 20 μmol/L) and lipopolysaccharides (LPS, 1 µg/mL) on the viability of BV-2 cells were determined by MTT assay. After the transfection of C1ql3 overexpression plasmid, C1ql3 expression, IL-1β and IL-6 levels, and the number of CD16+/32+ and CD206+ cells were determined by qRT-PCR, ELISA and flow cytometry, respectively. ResultC1ql3 expression was down-regulated in microglia after the curcumin treatment. Curcumin treatment could alleviate the TBI-induced brain injury in mice, reduce IL-1β and IL-6 levels, promote M2 polarization of microglia, and decrease C1ql3 protein expression. For BV-2 cells, curcumin treatment had no significant toxic effect on cell viability, but reversed the effect of LPS on cells, while C1ql3 overexpression counteracted the effect of curcumin. ConclusionCurcumin induces M2 microglia polarization through down-regulating C1ql3 expression, which may become a new treatment method for TBI. Availability of data and materialsThe analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Analysis of IL-10 and IL-35 in dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

The association between immunoregulatory cytokines, such as interleukin (IL)-10 or IL-35, and dipeptidyl peptidase-4 inhibitor (DPP4i)-related bullous pemphigoid (BP) has not been evaluated. Serum IL-10 and IL-35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i-related and 33 DPP4i-unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i-related BP and six randomly sampled patients with DPP4i-unrelated BP). Patients with DPP4i-related BP had lower levels of serum eosinophils (DPP4i-related vs. DPP4i-unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/μL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL-10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL-35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti-BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL-10 and IL-35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i-related BP.

Increased Peripheral Inflammation Is Associated With Structural Brain Changes and Reduced Blood Flow in People With Virologically Controlled HIV.

While antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH receiving ART, thereby contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, underlying mechanisms remain elusive. Our cohort consisted of PWH with ART adherence and viral suppression ( < 50 copies/mL; N = 173). Measurements included immune cell markers of overall immune health (CD4/CD8 T-cell ratio) and myeloid inflammation (CD16+ monocytes), plasma markers of inflammatory status (soluble CD163 and CD14), and structural and functional neuroimaging (volume and cerebral blood flow [CBF], respectively). Decreased CD4/CD8 ratios correlated with reduced brain volume, and higher levels of inflammatory CD16+ monocytes were associated with reduced brain volume in total cortex and gray matter. An increase in plasma soluble CD14-a marker of acute peripheral inflammation attributed to circulating microbial products-was associated with reduced CBF within the frontal, parietal, temporal, and occipital cortices and total gray matter. CD4/CD8 ratio and number of CD16+ monocytes, which are chronic immune cell markers, are associated with volumetric loss in the brain. Additionally, this study shows a potential new association between plasma soluble CD14 and CBF.

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

BackgroundIntra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA).MethodsTotal number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage.ResultsForty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively.ConclusionInter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group.Trial registration: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46), IRCT20080728001031N23. Registered 24 April 2018.