Peripheral Immune Status Research Articles

Alterations in intratumoral and peripheral immune status in recurrent gliomas and their prognostic implications for patients underwent reoperation

BackgroundReoperation is a treatment option for recurrent gliomas, yet factors impacting survival following reoperation remain poorly defined. Tumor immunity is profoundly associated with disease progression. Here, we analyze the immune status characteristics and their prognostic implications in recurrent gliomas. MethodsIntratumoral and peripheral immune characteristics between primary and recurrent gliomas were compared by conducting immunohistological staining and hematological examination with our in-house samples, and analyzing bulk and single-cell sequencing data from publicly available sources. Survival analysis was conducted to identify immunological markers with prognostic significance. ResultsWe observed a significant reduction in peripheral lymphocyte count, while an elevation in neutrophil-to-lymphocyte ratio (NLR) and red cell distribution width-to-platelet ratio (RPR) in patients with recurrent gliomas than in newly-diagnosed patients. Higher NLR and RPR indicated worse survival following reoperation in recurrent patients. Transcriptomic and immunohistological analysis showed an increased infiltration of tumor-associated macrophages (TAMs) and CD8+ T cell in recurrent gliomas compared to primary gliomas in both IDH-wildtype and mutant subtypes. Moreover, the abundance of TAMs emerged as an independent indicator for an inferior prognosis in recurrent gliomas. Single-cell profiling revealed a significant heterogeneity in the phenotypes of TAMs between primary and recurrent gliomas. Notably, TAMs enriched in recurrent gliomas exhibited elevated expression of interferon-γ-induced genes, multiple immunosuppressive molecules (TGFB1, CD276), and increased activity in glycose and lipid metabolism, indicating metabolic reprogramming. ConclusionRecurrent gliomas demonstrate augmented immune cell infiltration, but they fail to overcome TAMs-induced immunosuppression. Immunosuppressive indices, including TAM abundance, peripheral NLR and RPR, have prognostic implications for recurrent gliomas.

Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce. We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy. This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR. The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively). Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.

Abstract PO2-15-03: Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin

Abstract Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. We quantified the relative effects of NLR and PLR on survival in patients with recurrent/stage IV BC and evaluated their clinical prognostic value. This retrospective study included 156 patients with recurrent/stage IV BC who received eribulin monotherapy at Saitama Medical University International Medical Center. We examined clinicopathological features (peripheral blood findings and biochemical liver and kidney function test results) and conducted univariate and multivariate analyses of the overall survival (OS). The 156 eribulin-treated patients had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) &amp;gt;1500/uL, NLRs &amp;lt; 3.0, and PLRs &amp;lt; 150 had significantly longer OS than those with lower ALCs, and higher NLR and PLRs (median OS, 25.5 vs. 15.5 months; p&amp;lt; 0.01; 20.3 vs. 13.6 months, P&amp;lt; 0.01; and 29.2 vs. 14.8 months; P&amp;lt; 0.001, respectively). Patients with anemia (hemoglobin &amp;lt; 10 g/dL) or liver dysfunction (albumin-bilirubin grade 2/3) had significantly shorter OS than those without (P&amp;lt; 0.001, respectively). Multivariate analysis revealed low albumin-bilirubin grade (P&amp;lt; 0.001), high hemoglobin (P&amp;lt; 0.01), and low PLR (P&amp;lt; 0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia, and liver dysfunction might be factors associated with prolonged OS in patients with recurrent/stage IV BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing. Citation Format: Hiroko Shimada, Kazuo Matsuura, Shunsuke Kohyama, Aya Asano, Masahiro Ohara, Hiroshi Ishiguro, Akihiko Osaki, Toshiaki Saeki. Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-03.

CHARACTERISTICS OF PERIPHERAL BLOOD INDICATORS AND IMMUNE STATUS IN PATIENTS WITH COINFECTED INFLUENZA AND COVID-19

The new coronavirus infection has played a significant role in the structure of acute respiratory diseases [1,2], and in combination with influenza, it changes not only the clinical picture, but also changes the laboratory parameters of the disease, primarily indicators of peripheral blood and immune status. The paper presents the features of the clinical course of coinfection, as well as the results of the parameters of the immune status. Based on the data obtained, the risk of developing fibrosis in infected patients was assessed in comparison with control groups.

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment.

Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume. High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses. Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells. High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma – knowledge obtained from the CheckRad-CD8 trial

PurposeIndividual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. MethodsThe peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. ResultsThe tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. ConclusionsOur analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

The effects of aging, sex, and tumor burden on the peripheral blood immune cell profile and absolute counts.

Background: To better assess the peripheral immune status and aid in the early diagnosis and prognosis of tumors, we compared the proportion and absolute counting of peripheral immune cell subsets in healthy individuals and tumor patients of varying ages, taking into account the impact of sex and tumor metastasis. Methods: We used peripheral blood mononuclear cell (PBMC) samples from 520 patients with various tumor types and 109 healthy volunteers. The absolute numbers of lymphocytes and monocytes were identified by an automated blood analyzer, and multi-parameter flow cytometry was used to examine the subsets of natural killer (NK) cells (CD3-CD16+CD56+), T cells (CD3+CD4+/CD8+), and mononuclear cells (CD14+) in PBMC. Results: The percentage of T cells (CD3+) in peripheral blood mononuclear cells (PBMC) was 55.83% VS 45.54% (P<0.0001) between healthy volunteers and tumor patients, showing a significant downward trend. Meanwhile, the percentages of monocytes (CD14+) and NK cells (CD3-CD16+CD56+) showed a significant upward trend. Single factor or multifactor analysis yielded identical findings on the proportion of PBMC between healthy individuals and patients with different malignancies, considering the three confounding variables of age, sex, and tumor metastasis. Conclusion: The proportion and absolute counting of acquired immune T cells, innate immune NK cells, and monocytes in PBMCs all exhibit substantial changes between cancer patients and healthy individuals, and the differences are influenced by age, sex, and tumor progression.

BIOM-42. LONGITUDINAL IMMUNE PROFILES OF LOWER GRADE ADULT GLIOMA PATIENTS

Abstract Immune dysregulation is a known characteristic of glioma, however there is little known about the peripheral immune status of lower-grade (LrGG) glioma patients across the course of disease. Using immunomethylomic (deconvoluted blood DNA methylation) data from the UCSF Immune Profiles Study, we explore changes in patient peripheral blood immune cell profiles in newly diagnosed and recurrent LrGG patients. For patients receiving radiation (RT) and temozolomide (TMZ) (n = 75), blood is collected pre-RT/TMZ, post-RT/TMZ, before, during, and after adjuvant TMZ (if applicable). For patients followed only by MRI (n = 53) and those with other treatment plans (n = 67), blood is collected at MRIs, and if applicable, before radiation. For all patients, blood is also collected before new treatment intervention. For patients (LrGG IDH mutated) with paired pre- and post-surgery samples (n = 139), we observed a significant post-surgery increase in the count of memory B-cells (p = 1.7e-5), neutrophils (p = 0.0001), basophils (p = 8.7e-5), monocytes (p = 0.0001), and T-regulatory cells (p = 0.0001) along with a significant decrease in natural killer cells (p = 0.0003). Treatment was also associated with altered patient immune profiles. The use of dexamethasone was associated with an increased count of B-memory (p = 0.0001) and B-naïve cells (p = 0.0001), monocytes (p = 2.1e-5), and neutrophils (p = 3.7e-6) post-surgery. Patients receiving chemoradiation (n = 12) exhibited significant and temporally sustained decreases in B-memory (p &amp;lt; 0.0001), B-naïve (p = 0.005), CD4 naïve cells (p = 0.002), and in neutrophils (p = 0.001). Patient follow-up, data collection, and further analyses are ongoing. These results shed light on the dynamic and variable immune changes in LrGG patients and provide a guide for future prognostic and therapeutic studies.

A relation between specific immune status indicators and activity of “lipid peroxidation — antioxidant defense” system in COVID-19 neonates

The 2019 coronavirus infection (COVID-19) has not been considered as a solved issue for public health. Pregnant women and newborns are specifically vulnerable to COVID-19 infection compared to older children and healthy young adults. Virtually no data on relation between diverse arms of immunity in patients in neonatal period and coronavirus infection are available. The obtained results can contribute to a better understanding of the pathogenetic mechanisms on reactivity of immune processes in young patients and corresponding formation of approaches for prevention and correction of such disorders. The aim of the study was to determine magnitude of specific altered parameters in immune system and their relation with lipid peroxidation parameters in COVID-19 newborns. Two groups of newborns (mean age 43.1 days) were examined: SARS-CoV-2-positive (COVID-19 patients, n = 44) and negative (control group, n = 80) PCR test of nasopharyngeal swab. All newborns were assessed for specific indicators of peripheral blood immune status and lipid peroxidation activity. The concentration of Th1-pro-inflammatory cytokines and Th2-anti-inflammatory interleukins was assessed by enzyme immunoassay method (a panel of monoclonal antibodies). Spectrophotometric, fluorometric and enzyme immunoassay methods to evaluate the lipid peroxidation system were used. According to our data, newborns with COVID-19 vs. healthy newborns had decreased CRP, pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8, and anti-inflammatory factor (IL-4). Change in lipid peroxidation system in children with COVID-was 19 related to higher level of DC, KD and CT, TBARs, increased SOD activity and reduced GPO. Numerous intersystem dependencies in the group of newborns with COVID-19 (CRP Total AOA, IL-4 KD and CT, IL-4 TBARs, IL-4 Total AOA, IL-4 SOD, IL-8 SOD, IFN GSH) were noted. It can be concluded that in newborns with COVID-19, changes in the immune system are nonspecific and are accompanied by an increased intensity of lipid peroxidation reactions against the background of reduced values of pro- and anti-inflammatory cytokines. These results may contribute to a more accurate assessment of intensity and dynamics of emerging neonatal coronavirus infection, which should be an important arm in preventing subsequent complications.

Prognostic value of systemic inflammatory response in early-stage triple-negative breast cancer.

e14562 Background: Among breast cancer (BC) triple-negative (TN) subtype is the most immunogenic. Host and systemic immune response characterised by tumor-infiltrating lymphocytes (TILs) and immune cells in peripheral blood shape the net anti-tumor immune status. The systemic immune-inflammation index (SII) represents an effective indicator of the peripheral immune status. To date, TILs and SII have been largely examined separately. Therefore, in the present study, we investigated the prognostic value and relationship between pretreatment TILs and SII in a large number of unselected patients (pts) with early (e) stage TNBC. Methods: A total of 301 consecutive eTNBC pts treated with curative intent at Oncology Institute Ljubljana from January 2000 till August 2007 were investigated. Histopathological and clinical data were obtained retrospectively from the medical records. TILs were scored as intensive vs others. SII was determined by platelet × neutrophil/lymphocyte. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The optimal cut-off value of SII was 675 and was evaluated using the receiver operating characteristic (ROC) curve. Results: The median follow-up period was 17,6 years (16.9-18.3), and the entire cohort`s 10-year DFS was 67.5% and 10-year OS 72.1%. The median age was 54 (53-57) years. Most pts were diagnosed node negative (40.7%), with larger tumors (≥ 2 cm, 57.1%), grade 3 (83.5%) and underwent perioperative chemotherapy (cht) (81%). Patients with positive lymph nodes (LN) had higher SII (r=0.21, p=0.003), no correlation between LN and TILs was found. Patients with higher TILs had significantly better OS (HR: 0.40, 95% CI 0.37-0.97, p=00.004), and lower SII predicted significantly better DFS and OS (HR for DFS: 1.65 95% CI 1,03-2.67, p=0.038, HR for OS: 1.72, 95% CI 1.11-2.65, p=0,015). In multivariate analysis, positive LN status retained its independent prognostic value for worse DFS and positive LN and higher SII for worse OS. Conclusions: Our data confirms important role of systemic immune response in the prognosis of eTNBC. The survival of these pts is significantly influenced by the pretreatment SII and TILs, the prognostic value of SII seems to be stronger in our cohort. However, positive lymph node status remains the strongest predictor for worse survival in eTNBC. [Table: see text]

Prognostic and recurrent significance of SII in patients with pancreatic head cancer undergoing pancreaticoduodenectomy.

To investigate the clinical significance of preoperative inflammatory status in patients with pancreatic head carcinoma (PHC), we performed a single-center study to assess it. We studied a total of 164 patients with PHC undergoing PD surgery (with or without allogeneic venous replacement) from January 2018 to April 2022. Systemic immune-inflammation index (SII) was the most important peripheral immune index in predicting the prognosis according to XGBoost analysis. The optimal cutoff value of SII for OS was calculated according to Youden index based on the receiver operating characteristic (ROC) curve and the cohort was divided into Low SII group and High SII group. Demographic, clinical data, laboratory data, follow-up data variables were obtained and compared between the two groups. Kaplan-Meier curves, univariable and multivariable Cox regression models were used to determine the association between preoperative inflammation index, nutritional index and TNM staging system with OS and DFS respectively. The median follow-up time was 16 months (IQR 23), and 41.4% of recurrences occurred within 1 year. The cutoff value of SII was 563, with a sensitivity of 70.3%, and a specificity of 60.7%. Peripheral immune status was different between the two groups. Patients in High SII group had higher PAR, NLR than those in Low SII group (P <0.01, <0.01, respectively), and lower PNI (P <0.01). Kaplan-Meier analysis showed significantly poorer OS and DFS (P < 0.001, <0.001, respectively) in patients with high SII. By using the multivariable Cox regression model, high SII (HR, 2.056; 95% CI, 1.082-3.905, P=0.028) was significant predictor of OS. Of these 68 high-risk patients who recurrence within one year, patients with widespread metastasis had lower SII and worse prognosis (P <0.01). High SII was significantly associated with poor prognosis in patients with PHC. However, in patients who recurrence within one year, SII was lower in patients at TNM stage III. Thus, care needs to be taken to differentiate those high-risk patients.

From the immune system to mood disorders especially induced by Toxoplasma gondii: CD4+ T cell as a bridge.

Toxoplasma gondii (T. gondii), a ubiquitous and obligatory intracellular protozoa, not only alters peripheral immune status, but crosses the blood-brain barrier to trigger brain parenchymal injury and central neuroinflammation to establish latent cerebral infection in humans and other vertebrates. Recent findings underscore the strong correlation between alterations in the peripheral and central immune environment and mood disorders. Th17 and Th1 cells are important pro-inflammatory cells that can drive the pathology of mood disorders by promoting neuroinflammation. As opposed to Th17 and Th1, regulatory T cells have inhibitory inflammatory and neuroprotective functions that can ameliorate mood disorders. T. gondii induces neuroinflammation, which can be mediated by CD4+ T cells (such as Tregs, Th17, Th1, and Th2). Though the pathophysiology and treatment of mood disorder have been currently studied, emerging evidence points to unique role of CD4+ T cells in mood disorder, especially those caused by T. gondii infection. In this review, we explore some recent studies that extend our understanding of the relationship between mood disorders and T. gondii.

A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

Neoadjuvant therapy (NAT) has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival, particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer. The role of peripheral immune components in predicting therapeutic responses has received limited attention. Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration. Peripheral immune index data were collected from 134 patients before and after NAT. Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes, respectively. Peripheral immune status with a greater number of CD3+ T cells before and after NAT, and a greater number of CD8+ T cells, fewer CD4+ T cells, and fewer NK cells after NAT was significantly related to a pathological complete response (P < 0.05). The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT (HR = 0.13, P = 0.008). Based on the results of logistic regression, 14 reliable features (P < 0.05) were selected to construct the machine learning model. The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches (AUC = 0.733). Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed. A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

Impact of body mass index on peripheral and uterine immune status in the window of implantation in patients with recurrent reproductive failure

This study aimed to investigate whether maternal obesity affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure classified according to their body mass index (BMI). A total of 228 repeated implantation failure (RIF) and 266 recurrent miscarriage (RM) patients were enrolled in the study and further subdivided into three groups according to their BMI: (i) normal weight (18.5≤ BMI <23); (ii) overweight (23≤ BMI <25); and (iii) obese (BMI ≥25). Peripheral blood and endometrium samples were collected in the mid-luteal phase before IVF treatment or natural pregnancy. Peripheral immunocytes were analyzed by flow cytometry, while uterine immune cells were subjected to immunohistochemistry. In RM patients, significantly increased peripheral helper T cells and decreased cytotoxic T cells, NK cells were observed in the obese group compared with the normal-weight group. Meanwhile, in the endometrium, the percentage of NK cell, macrophage cell, M2 macrophage cell, and Treg cell significantly reduced with increased BMI in RIF patients, and the percentage of NK cell and M2 macrophage cell significantly decreased with increased BMI in RM patients. In conclusion, obesity may cause endometrial immune disorder in recurrent reproductive failure women, but was only associated with the peripheral immune change in RM patients.

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma

BackgroundWe previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of...

High percentages of peripheral blood T-cell activation in childhood Hodgkin's lymphoma are associated with inferior outcome.

The aims of this study were to investigate the activation of T lymphocytes in peripheral blood from children with Hodgkin's lymphoma (HL) and explore their roles for prognosis in HL. A cohort of 52 newly diagnosed children with HL during the past 10 years was enrolled for analysis in this study. Peripheral blood samples of the patients were acquired before treatment in our hospital, and T-cell subsets were detected by a four-color flow cytometer. CD4+ T cells and CD4+/CD8+ T-cell ratio decreased significantly in patients with HL vs. healthy controls. CD8+ T cells, CD3+CD4+HLA-DR+ T cells, and CD3+CD8+HLA-DR+ T cells increased markedly in patients with HL vs. healthy controls. Receiver-operating characteristic (ROC) curve analysis showed that CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells each distinguished the high-risk group from the low- and intermediate-risk group. The area under the ROC curve for predicting high-risk patients was 0.795 for CD3+CD4+HLA-DR+ T cell and 0.784 for CD3+CD8+HLA-DR+ T cell. A comparison of peripheral blood T-cell subsets that responded differently to therapy showed significantly higher percentages of CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells in patients who achieved complete remission compared to those who did not achieve complete remission. In addition, high percentages of both CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells were associated with inferior event-free survival. Peripheral immune status may be related to disease severity in HL. CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells may be a novel indicator for risk stratification of HL and may be an independent risk factor for inferior outcome in childhood HL.

Pathological complete response to neoadjuvant chemoimmunotherapy correlates with peripheral blood immune cell subsets and metastatic status of mediastinal lymph nodes (N2 lymph nodes) in non-small cell lung cancer

BackgroundNeoadjuvant chemo-immunotherapy has got clinical benefits in parts of resectable non-small cell lung cancer (NSCLC) patients. The factors affecting the pathological response of NSCLC remain controversial. MethodsA retrospective study of 59 patients with resectable stage IIA-IIIB NSCLC who were treated with neoadjuvant chemo-immunotherapy was performed. The clinical characteristics were analyzed in the pathological complete response (pCR) group and the non-pCR group. The immune cell subsets in peripheral blood were detected by flow cytometry. ResultsBy analyzing the correlation between pathological response and clinical characteristics, we found that patients with N2 metastases were less effective in neoadjuvant chemo-immunotherapy (P = 0.001). Programmed death-ligand 1 (PD-L1) expression and treatment cycle were not related to pathological response (P > 0.05). Lower levels of total T cells, Th cells, and higher levels of NK cells in baseline were associated with pCR (P < 0.05). And during neoadjuvant chemo-immunotherapy, total T cells and activated T cells were significantly increased in patients with pCR (P < 0.05). ConclusionThe peripheral blood immune cell subsets and lymph node status were closely related to pathological response in patients with neoadjuvant chemo-immunotherapy. No significant correlation was found between pathologic response and PD-L1 expression.

Insights from a Rapidly Implemented COVID-19 Biobank Using Electronic Consent and Informatics Tools.

Biobanking during the COVID-19 pandemic presented unique challenges regarding patient enrollment, sample collection, and experimental analysis. This report details the ways in which we rapidly overcame those challenges to create a robust database of clinical information and patient samples while maintaining clinician and researcher safety. We developed a pipeline using REDCap (Research Electronic Data Capture) to coordinate electronic informed consent, sample collection, immunological assay execution, and data analysis for biobanking samples from patients with COVID-19. We then integrated immunological assay data with clinical data extracted from the electronic health record to link study parameters with clinical readouts. Of the 193 inpatients who participated in this study, 138 consented electronically and 56 provided paper consent. We collected and banked blood samples to measure circulating cytokines and chemokines, peripheral immune cell composition and activation status, anti-COVID-19 antibodies, and germline gene polymorphisms. In addition, we collected DNA and RNA from nasopharyngeal swabs to assess viral titer and microbiome composition by 16S sequencing. The rapid spread and contagious nature of COVID-19 required special considerations and innovative solutions to biobank samples quickly while protecting researchers and clinicians. Overall, this workflow and computational pipeline allowed for comprehensive immune profiling of 193 inpatients infected with COVID-19, as well as 89 outpatients, 157 patients receiving curbside COVID-19 testing, and 86 healthy controls. We describe a novel electronic framework for biobanking and analyzing patient samples during COVID-19, and present insights and strategies that can be applied more broadly to other biobank studies.

Profiles of Proinflammatory Cytokines and T Cells in Patients With Tourette Syndrome: A Meta-Analysis.

BackgroundTic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients.MethodIn the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079).ResultsIn the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84).ConclusionWe provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration.

Poorer survival outcomes in patients with multiple versus single primary melanoma.

Given equivocal results related to overall survival (OS) for patients with multiple primary melanomas (MPMs) compared with those with single primary melanomas (SPMs) in previous reports, the authors sought to determine whether OS differs between these 2 cohorts in their center using their UPCI-96-99 database. Secondary aims were to assess the differences in recurrence-free survival (RFS). In a subset of patients, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed to assess disease-associated genes of interest. This retrospective case-controlled study included patients with MPMs and age-, sex-, and stage-matched controls with SPMs at a 1:1 ratio. Cox regression models were used to evaluate the effect of the presence of MPMs on death and recurrence. NanoString PanCancer Immune Profiling was used to assess peripheral blood immune status in patients. In total, 320 patients were evaluated. The mean patient age was 47years; 43.8% were male. Patients with MPMs had worse RFS and OS (P=.023 and P=.0019, respectively). The presence of MPMs was associated with an increased risk of death (hazard ratio [HR], 4.52, P=.0006), and increased risk of disease recurrence (HR, 2.17; P=.004) after adjusting for age, sex, and stage. The degree of tumor-infiltrating lymphocytes (TILs) was different between the first melanoma of MPMs and SPMs. Expression of CXCL6 and FOXJ1 was increased in PBMCs isolated from patients with MPMs. Patients with MPMs had worse RFS and OS compared with patients with SPMs. Immunologic differences were also observed, including TIL content and expression of CXCL6/FOXJ1 in PBMCs of patients with MPMs, which warrant further investigation.