Immune Responses In Cancer Patients Research Articles

Humoral immune response as an indicator for protection against Covid-19 after anti-SARS-COV2-booster vaccination in hematological and oncological patients.

Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.

Relationship between the white blood cell count and some lipid profile parameters in cancer patients with myocardial infarction

Hokkaido University (Tsumita T, 2022) researchers found that endothelial cells accumulate low-density lipoproteins (LDL) in tumor blood vessels. At the same time, the endothelium carries out neutrophil chemotaxis, which perform an immunosuppressive function contributing to cancer progression.Aim. To search for the relationship between the white blood cell (WBC) count and some lipid profile parameters in cancer patients with myocardial infarction (MI).Material and methods. We examined 319 patients who were treated at Dzhanelidze Research Institute of Emergency Medicine in 2018-2023, which were divided into three groups: MI in combination with an active cancer — 132 patients (Group I), MI+cancer in history — 58 patients (Group II), MI without cancer — 129 patients (Group III). Following laboratory data used in routine practice were assessed: WBC count, relative neutrophil count, total cholesterol, low-density lipoproteins.Results. Cancer patients with MI are characterized by higher WBC and neutrophil count than in other samples However, the total cholesterol level was significantly lower in this sample, and the LDL level was not significantly different. Patients with MI and previous cancer occupied an intermediate position between groups I and III in terms of studied parameters.Conclusion. In general, data on the role of cholesterol levels in cancer patients are contradictory. In particular, some studies have shown that elevated cholesterol levels are a potential risk factor for cancer. In our study, as in a number of others, no significant associations were identified between elevated cholesterol levels and the presence of cancer. Our study is a step towards understanding the connection between the cholesterol concentration and the immune response in cancer patients with MI.

Plasma EV-miRNAs as Potential Biomarkers of COVID-19 Vaccine Immune Response in Cancer Patients.

Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines.

A fragment-based algorithm for identifying pan-cancer differential methylation markers from cfDNA.

e22507 Background: Methylation-based sequencing has been developed as a promising approach for Multi-Cancer Early Detection (MCED). Conventionally, cancer-specific methylation markers were identified by comparing paired tumor and adjacent normal tissues using traditional algorithm DSS (Dispersion shrinkage for sequencing data). However, the clinical applicability is limited by the unsatisfactory sensitivity in early-stage disease. Hence, we included blood specific markers derived from paired tissue and blood samples and developed a novel fragment-based algorithm in cfDNA with a better signal to noise ratio (SNR) than DSS to improve the sensitivity of the assay. Methods: A total of 391 plasma samples and 433 tissue samples from 7 cancer types were subjected to whole genome bisulfite sequencing (WGBS) (Table). The proportion of stage I-III and stage IV was 3.5:1 among 7 cancer types. The average sequencing depth was 30X. For each bin, the proportion of fully methylated (M) / un-methylated (U) fragments, defined with methylation level ≥85% / ≤15%, was computed individually. One-sided Wilcoxon rank sum test was employed to test whether cancer cfDNA have significantly (FDR < 0.001) higher proportion of U/M fragments than control cfDNA. Results: To evaluate the performance of fragment-based algorithm in cfDNA, the false positive was assessed by resampling from healthy subjects. The healthy cfDNA were randomly assigned 20 times as pseudo case-control groups of 30 /170. The number of markers among healthy samples was recorded as NFalse Positive (NFP), while the number of markers between cancer and healthy samples was recorded as NPositive (NP). SNR was defined as (NP-NFP)/NFP. We calculated SNR using the fragment-based algorithm and achieved SNR of 135.2 for colorectal cancer, compared to SNR of 2.2 using DSS. The improved SNR was also reproduced in other cancer types. Concordance between plasma and tissue markers was 30.09%-95.92% (median 66.72%) among 7 cancer types, which was related to the proportion of ctDNA for each cancer type. Plasma markers which show weak signals in tissue are defined as blood-specific markers. These markers were enriched in immune-related pathways, suggesting a correlation to the immune response of cancer patients. Conclusions: We developed a novel fragment-based algorithm that achieves much higher SNR than DSS in cfDNA. We also identified blood-specific methylation markers which may improve the sensitivity of early cancer detection in clinical. [Table: see text]

The Ability of Clinically Relevant Chemotherapeutics to Induce Immunogenic Cell Death in Squamous Cell Carcinoma.

Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC. We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP), Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients. Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro, it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells. The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.

The Chemokine CXCL14 as a Potential Immunotherapeutic Agent for Cancer Therapy.

There is great enthusiasm toward the development of novel immunotherapies for the treatment of cancer, and given their roles in immune system regulation, chemokines stand out as promising candidates for use in new cancer therapies. Many previous studies have shown how chemokine signaling pathways could be targeted to halt cancer progression. We and others have revealed that the chemokine CXCL14 promotes antitumor immune responses, suggesting that CXCL14 may be effective for cancer immunotherapy. However, it is still unknown what mechanism governs CXCL14-mediated antitumor activity, how to deliver CXCL14, what dose to apply, and what combinations with existing therapy may boost antitumor immune responses in cancer patients. Here, we provide updates on the role of CXCL14 in cancer progression and discuss the potential development and application of CXCL14 as an immunotherapeutic agent.

Trends in Anti-Tumor Effects of Pseudomonas aeruginosa Mannose-Sensitive-Hemagglutinin (PA-MSHA): An Overview of Positive and Negative Effects

Cancer is a leading cause of death worldwide, for which finding the optimal therapy remains an ongoing challenge. Drug resistance, toxic side effects, and a lack of specificity pose significant difficulties in traditional cancer treatments, leading to suboptimal clinical outcomes and high mortality rates among cancer patients. The need for alternative therapies is crucial, especially for those resistant to conventional methods like chemotherapy and radiotherapy or for patients where surgery is not possible. Over the past decade, a novel approach known as bacteria-mediated cancer therapy has emerged, offering potential solutions to the limitations of conventional treatments. An increasing number of in vitro and in vivo studies suggest that the subtype of highly virulent Pseudomonas aeruginosa bacterium called Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) can successfully inhibit the progression of various cancer types, such as breast, lung, and bladder cancer, as well as hepatocellular carcinoma. PA-MSHA inhibits the growth and proliferation of tumor cells and induces their apoptosis. Proposed mechanisms of action include cell-cycle arrest and activation of pro-apoptotic pathways regulated by caspase-9 and caspase-3. Moreover, clinical studies have shown that PA-MSHA improved the effectiveness of chemotherapy and promoted the activation of the immune response in cancer patients without causing severe side effects. Reported adverse reactions were fever, skin irritation, and pain, attributed to the overactivation of the immune response. This review aims to summarize the current knowledge obtained from in vitro, in vivo, and clinical studies available at PubMed, Google Scholar, and ClinicalTrials.gov regarding the use of PA-MSHA in cancer treatment in order to further elucidate its pharmacological and toxicological properties.

Circulating IL-6 and not its circulating signaling components sIL-6R and sgp130 demonstrate clinical significance in NSCLC patients treated with immune checkpoint inhibitors.

Introduction: Clinical roles of plasma IL-6 levels have been reported in patients with various cancers, including non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (ICIs). However, the roles of other IL-6 signaling components, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130), in the plasma have not been elucidated. Methods: Blood was collected from 106 patients with NSCLC before initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Plasma levels of IL-6, sIL-6R, sgp130, and their complexes were assessed by Cox regression hazard model to evaluate their clinical significance. The clinical role of IL-6 or IL-6R genetic polymorphisms was also analyzed. Results: Cox regression analysis showed that higher plasma IL-6 levels significantly predicted unfavorable overall survival (OS; hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.05-1.68, p = 0.012) in NSCLC patients treated with ICIs. However, plasma sIL-6R and sgp130 levels showed no prognostic significance (p = 0.882 and p = 0.934, respectively). In addition, the estimated concentrations of binary IL-6:sIL-6R and ternary IL-6:sIL-6R:sgp130 complexes and their ratios (binary/ternary complex) were not significantly associated with OS (p = 0.647, p = 0.727, and p = 0.273, respectively). Furthermore, the genetic polymorphisms of IL-6 (-634G>C) and IL-6R (48892A>C) showed no clinical role by Kaplan-Meier survival analysis (p = 0.908 and p = 0.639, respectively). Discussion: These findings demonstrated the clinical significance of plasma levels of IL-6, but not of other IL-6 signaling components, sIL-6R and sgp130, suggesting that classical IL-6 signaling, but not trans-signaling, may be related to anti-tumor immune responses in cancer patients treated with ICIs.

Fully closed and automated enrichment of primary blood dendritic cells for cancer immunotherapy.

Dendritic cell (DC) vaccination is a promising approach to induce tumor-specific immune responses in cancer patients. Until recently, most DC vaccines were based on in vitro-differentiated monocyte-derived DCs. However, through development of efficient isolation techniques, the use of primary blood dendritic cell subsets has come within reach. Manufacturing of blood-derived DCs has multiple advances over monocytes-derived DCs, including more standardized isolation and culture protocols and shorter production processes. In peripheral blood, multiple DC subsets can be distinguished based on their phenotype and function. Plasmacytoid DC (pDC) and myeloid/conventional DCs (cDC) are the two main DC populations, moreover cDC can be further subdivided into CD141/BDCA3+ DC (cDC1) and CD1c/BDCA1+ DC (cDC2). In three separate clinical DC vaccination studies in melanoma and prostate cancer patients, we manufactured DC vaccines consisting of pDCs only, cDC2s only, or a combination of pDC and cDC2s, which we called natural DCs (nDC). Here, we describe a fully closed and automated GMP-compliant method to enrich naturally circulating DCs and present the results of enrichment of primary blood DCs from aphaeresis products of 8 healthy donors, 21 castrate-resistant prostate cancer patients, and 112 stage III melanoma patients. Although primary blood DCs are relatively scarce in aphaeresis material, our results show that it is feasible to isolate highly pure pDC, cDC2, or nDC with sufficient yield to manufacture DC vaccines for natural DC-based immunotherapy.

Myeloid-derived suppressor cells and tolerogenic dendritic cells are distinctively induced by PI3K and Wnt signaling pathways

Imbalanced immune responses are a prominent hallmark of cancer and autoimmunity. Myeloid cells can be overly suppressive, inhibiting protective immune responses or inactive not controlling autoreactive immune cells. Understanding the mechanisms that induce suppressive myeloid cells, such as myeloid-derived suppressor cells (MDSCs) and tolerogenic dendritic cells (TolDCs), can facilitate the development of immune-restoring therapeutic approaches. MDSCs are a major barrier for effective cancer immunotherapy by suppressing antitumor immune responses in cancer patients. TolDCs are administered to patients to promote immune tolerance with the intent to control autoimmune disease. Here, we investigated the development and suppressive/tolerogenic activity of human MDSCs and TolDCs to gain insight into signaling pathways that drive immunosuppression in these different myeloid subsets. Moreover, monocyte-derived MDSCs (M-MDSCs) generated invitro were compared to M-MDSCs isolated from head-and-neck squamous cell carcinoma patients. PI3K-AKT signaling was identified as being crucial for the induction of human M-MDSCs. PI3K inhibition prevented the downregulation of HLA-DR and the upregulation of reactive oxygen species and MerTK. In addition, we show that the suppressive activity of dexamethasone-induced TolDCs is induced by β-catenin-dependent Wnt signaling. The identification of PI3K-AKT and Wnt signal transduction pathways as respective inducers of the immunomodulatory capacity of M-MDSCs and TolDCs provides opportunities to overcome suppressive myeloid cells in cancer patients and optimize therapeutic application of TolDCs. Lastly, the observed similarities between generated- and patient-derived M-MDSCs support the use of invitro-generated M-MDSCs as powerful model to investigate the functionality of human MDSCs.

Liver metastases across cancer types sharing tumor environment immunotolerance can impede immune response therapy and immune monitoring

BackgroundHepatic immune tolerance might contribute to the development of therapeutic resistance to immunotherapy. However, addressing this issue is challenging since the efficacy of immunotherapy in the context of liver metastasis (LM) remains poorly studied. Here, we aimed to establish an LM common immune feature (LMCIF) score to quantify the characteristics of LM immunotolerance across cancer types for assisting clinical disease management. MethodsLarge-scale clinical data were collected to identify the prognosis of LM. Multi-omics datasets of metastatic cancers with LM special immune-related pathways (LMSIPs) from the Molecular Signatures Database (MSigDB)were used to obtain an LMCIF cluster. Based on differential expression genes (DEGs), a novel LMCIF score for the LMCIF cluster was constructed. In addition, multi-omics, and immunohistochemistry (IHC) data from the public and in-house cohorts were used to explore the features of LM, and LMCIF score. ResultsPatients with LM had a worse prognosis and significantly lower infiltration of immune cells than patients with metastasis to other organs when analyzed with combined clinical and RNA sequencing data. After extracting the LMCIF cluster from 373 samples by utilizing 29 LMSIPs and validating them in a microarray cohort, an LMCIF score was established to confirm the role of the immunosuppressive environment as a contributor to the poor prognosis of LM across cancer types. Moreover, this LMCIF score could be used to predict the immune response of cancer patients undergoing immunotherapy. Finally, we identified that the majority of the 31 LMCIF genes exhibited a negative correlation with TME cells in LM patients, one of them, KRT19, which possessed the strongest positive correlation with LMCIF score, was confirmed to have an immunosuppressive effect through IHC analysis. ConclusionsOur results suggest that LM across cancer types share similar immunological profiles that induce immunotolerance and escape from immune monitoring. The novel LMCIF score represents a common liver metastasis immune cluster for predicting immunotherapy response, the results of which might benefit clinical disease management.

Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore.

The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists' T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). The standardized IS assay outperformed expert pathologists' T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.

Aging, Immunity and Cancer

Abstract Our studies have shown that breast cancer patients receiving CBSM (Cognitive Behavioral Stress Management) have less stress and inflammation and better immune response, e.g. antibody response to influenza vaccine. More recently immune (B lymphocyte, antibodies) and metabolic (higher) conditions were characterized. We previously showed the stress reduction group had better long term (11 year) survival. Currently we are further analyzing negative and positive contributors to immune response in cancer patients including age and body mass. Supported by grants from NIH (R01 AI)", Florida Breast Cancer and SCCC

A combined analysis of bulk and single-cell sequencing data reveals metabolic enzyme, pyruvate dehydrogenase E1 subunit beta (PDHB), as a prediction biomarker for the tumor immune response and immunotherapy

Pyruvate dehydrogenase E1 subunit beta (PDHB) is located in mitochondria and catalyzes the conversion of glucose-derived acetyl-CoA. The detailed roles of PDHB in human cancers is unclear. Here, through comprehensive bioinformatics analysis, we found that PDHB was aberrantly expressed in multiple human cancers and is associated with patients' clinical stage. The abnormal expression of PDHB was related to the prognostic values of cancers, such as kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). The Wanderer database with clinical data from Cancer Genome Atlas (TCGA) showed a significant correlation between PDHB expression and the pathologic stage of KIRP patients. We also evaluated the mutation profiles of PDHB in pan-cancer, and showed its roles on the patients’ prognosis. At last, from several immunity algorithms, we demonstrated that the expression of PDHB was correlated with the infiltration of various immune cells in pan-cancer. Moreover, the aberrant PDHB had effects on the response to immune checkpoint inhibitors in cancer patients, such as anti-PD-1. Taken together, our study demonstrated the prognostic values of PDHB in pan-cancers. PDHB may be a potential molecular marker to predicting the immune response in cancer patients.

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy.

An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as "concomitant immunity" suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression. This review updates latest information about immunosuppression by the TME and discusses mechanisms of how oncolytic viruses, in particular NDV, and cellular immunotherapy can counteract the immunosuppressive effect of the TME. With regard to cellular immunotherapy, the review presents pre-clinical studies of post-operative active-specific immunotherapy and of adoptive T cell-mediated therapy in immunocompetent mice. Memory T cell (MTC) transfer in tumor challenged T cell-deficient nu/nu mice demonstrates longevity and functionality of these cells. Graft-versus-leukemia (GvL) studies in mice demonstrate complete remission of late-stage disease including metastases and cachexia. T cell based immunotherapy studies with human cells in human tumor xenotransplanted NOD/SCID mice demonstrate superiority of bone marrow-derived as compared to blood-derived MTCs. Results from clinical studies presented include vaccination studies using two different types of NDV-modified cancer vaccine and a pilot adoptive T-cell mediated therapy study using re-activated bone marrow-derived cancer-reactive MTCs. As an example for what can be expected from clinical immunotherapy against tumors with an immunosuppressive TME, results from vaccination studies are presented from the aggressive brain tumor glioblastoma multiforme. The last decades of basic research in virology, oncology and immunology can be considered as a success story. Based on discoveries of these research areas, translational research and clinical studies have changed the way of treatment of cancer by introducing and including immunotherapy.

Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention.

The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.

Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment

BackgroundPatients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections.Patients and methodsPatients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster.ResultsFifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19.ConclusionsAn mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.

Immunogenicity evaluation of ChAdox1 nCov-19 (AZD1222) vaccine in solid cancer patients in Chulabhorn Hospital

ABSTRACT Introduction Cancer patients are more vulnerable to coronavirus disease 2019 (COVID-19) owing to their compromised immune status. However, data regarding COVID-19 vaccine safety and immune response in cancer patients are scarce. Method This prospective, age- and sex-matched, single-center cohort study included 61 cancer patients and 122 healthy control participants. Seropositivity was defined as anti-S IgG titer >0.8 units/ml. Primary end point was seroconversion rate of immunoglobulin (Ig)G antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein (anti-S IgG) in cancer patients vs. healthy control participants following the second dose of COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results After the second-dose vaccination, there was no difference in seropositivity rate between groups (57 [93.44%] patients with cancer vs. 121 [99.18%] control participants; geometric mean ratio [GMR]: 0.39; 95%CI: 0.01–10.46; p-value = 0.571). In contrast, after the first-dose vaccination, the seropositivity rate was significantly lower in the cancer patients than in the control participants (50/61 [81.97%] vs. 121/122 [99.18%]; GMR: 0.07; 95%CI: 0.01–0.71; p = 0.025). The median anti-S IgG titer after the first-and second dose vaccination were not significantly different between groups. Female sex was significantly associated with a higher anti-S IgG titer. 5FU- and taxane-based chemotherapy regimens were associated with a lower IgG titer. Side effects of vaccination were tolerable. Conclusions The anti-S IgG seropositivity rate after completing the second vaccine dose did not differ between the cancer patients and control participants. However, the anti-S IgG seropositivity rate after the first-dose vaccination was lower in cancer patients.

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma

BackgroundCancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated.MethodsIn this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells.ResultsThe results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis.ConclusionsIn conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

Identification and molecular characterization of simian endogenous retrovirus in Macaca fascicularis and Macaca nemestrina from captive breeding facilities in Bogor, Indonesia.

Background and Aim:Endogenous retroviruses (ERVs) found in all vertebrates, including non-human primates (NHPs), are known to be genetically inherited. Thus, recent studies have explored ERVs for human immunodeficiency virus vaccine development using human ERV (HERV) due to the hypervariability of exogenous retroviruses which cause conventional vaccines to be ineffective. HERV was also found to be able to induce an immune response in cancer patients. This study aimed to identify and molecularly characterize ERVs from Indonesian NHPs: Macaca fascicularis and Macaca nemestrina. Then, we described the phylogenetic relationship of these isolates with those of the simian ERVs (SERVs) characterized in other species and countries.Materials and Methods:First, 5 mL of whole blood samples was taken from 131 long-tailed macaques and 58 pig-tailed macaques in captive breeding facilities at Bogor, Indonesia, for DNA extraction. Next, the DNA samples were screened using the SYBR Green real-time polymerase chain reaction (PCR) technique with specific primers for env (simian retroviruses [SRV]1-5 7585U19 and SRV1-5 7695L21). Positive SERV results were those with cycle threshold (CT) values < 24 (CT < 24) and melting temperature (TM) ranges of 80°C–82°C. Then, whole-genome nucleotide sequences from two pig-tailed macaques samples detected as positive SERV were generated using a nucleic acid sequencing technique which utilized the walking primer method. Subsequently, the sequences were analyzed using bioinformatics programs, such as 4Peaks, Clustal Omega, and BLAST (NCBI). Subsequently, a phylogenetic tree was constructed using the neighbor-joining method in MEGA X.Results:SYBR Green real-time PCR amplification results indicated that SERV (Mn B1 and Mn B140910)-positive samples had CT values of 22.37–22.54 and TM of 82°C. Moreover, whole-genome sequences resulted in 7991 nucleotide sequences, comprising long terminal repeat, gag, pro, pol, and env genes identical between the sequenced samples. Furthermore, the phylogenetic tree results indicated that both samples from M. nemestrina had 99%–100% nucleotide identities to the Mn 92227 sample identified at the National Primate Center University of Washington (NaPRC UW) which was imported from Indonesia in 1998, confirmed as a novel SERV strain. The phylogenetic tree results also indicated that although SERV whole-genome nucleotide and env amino acid sequences were clustered with SRV-2 (identity values of 82% and 79%, respectively), they had a 99%–100% nucleotide identity to Mn 92227. Meanwhile, the gag, pro, and pol amino acids were clustered with SRV-1, SRV-3, SRV-4, SRV-5, SRV-8, and SERV/1997, with 82% and 88% identity values.Conclusion:Based on the SYBR Green real-time PCR profiles generated, similarities with Mn 92227 were observed. Subsequent phylogenetic analysis confirmed that both samples (Mn B1 and Mn B140919) from pig-tailed macaques in the country of origin were novel SERV strains at NaPRC UW. Therefore, it could be used in biomedical research on ERVs.