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Aberrant alteration of peripheral B lymphocyte subsets in hepatocellular carcinoma patients.

ABSTRACT: Although B lymphocytes are widely known to participate in the immune response, the conclusive roles of B lymphocyte subsets in the antitumor immune response have not yet been determined. Single-cell data from GEO datasets were first analyzed, and then a B cell flow cytometry panel was used to analyze the peripheral blood of 89 HCC patients and 33 healthy controls recruited to participate in our research. Patients with HCC had a higher frequency of B10 cells and a lower percentage of MZB cells than healthy controls. And the changes in B cell subsets might occur at an early stage. Moreover, the frequency of B10 cells decreased after surgery. Positively correlated with B10 cells, the elevated IL-10 level in HCC serum may be a new biomarker in HCC identification. For the first time, our results suggest that altered B cell subsets are associated with the development and prognosis of HCC. Increased B10 cell percentage and IL-10 in HCC patients suggest they might augment the development of liver tumors. Hence, B cell subsets and related cytokines may have predictive value in HCC patients and could be potential targets for immunotherapy in HCC.

SUBMITTER: Wu J

PROVIDER: S-EPMC9925981 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Aberrant alteration of peripheral B lymphocyte subsets in hepatocellular carcinoma patients.

Wu Jiaoxiang J Wang Yue Y Bai Shihao S Sun Hanxiao H Zhang Jie J Shu Jie J Wang Yajie Y Tan Meiyu M Zhou Lida L Huang Biao B Pan Qiuhui Q Sheng Huiming H

International journal of medical sciences 20230122 2

Although B lymphocytes are widely known to participate in the immune response, the conclusive roles of B lymphocyte subsets in the antitumor immune response have not yet been determined. Single-cell data from GEO datasets were first analyzed, and then a B cell flow cytometry panel was used to analyze the peripheral blood of 89 HCC patients and 33 healthy controls recruited to participate in our research. Patients with HCC had a higher frequency of B10 cells and a lower percentage of MZB cells th ...[more]

PMID: 36794164

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Project description:BackgroundAlthough peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear.MethodsWe prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features.ResultsWe found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05).ConclusionCirculating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Project description:ObjectiveThere is a high incidence of delirium among patients with organ dysfunction undergoing cardiac surgery who need critical care. This study aimed to explore the risk factors for delirium in critically ill patients undergoing cardiac surgery and the predictive value of related risk factors.MethodsWe conducted a prospective observational study on adult critically ill patients who underwent cardiac surgery between January 2019 and August 2021. Patients were consecutively assigned to delirium and non-delirium groups. Univariate analysis and multivariate logistic analysis were used to determine the risk factors for delirium. Receiver operating characteristic curves and a nomogram were used to identify the predictive value of related risk factors.ResultsDelirium developed in 242 of 379 (63.9%) participants. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were 14.2 ± 5.6 and 18 ± 8.4, respectively. Patients with delirium had longer cardiopulmonary bypass time (149.6 ± 59.1 vs. 126.7 ± 48.5 min, p < 0.001) and aortic cross-clamp time (98.7 ± 51.5 vs. 86.1 ± 41.6 min, p = 0.010) compared with the non-delirium group. The area under the curve was 0.824 for CD4+ T cell count and 0.862 for CD4/CD8 ratio. Multivariate analysis demonstrated that age [odds ratio (OR) 1.030, p = 0.038], duration of physical restraint (OR 1.030, p < 0.001), interleukin-6 (OR 1.001, p = 0.025), CD19+ B cell count (OR 0.996, p = 0.016), CD4+ T cell count (OR 1.005, p < 0.001) and CD4/CD8 ratio (OR 5.314, p < 0.001) were independent risk factors for delirium. A nomogram revealed that age, cardiopulmonary bypass duration, CD4+ T cell count and CD4/CD8 ratio were independent predictors of delirium.ConclusionAge, duration of physical restraint, CD4+ T cell count and CD4/CD8 ratio were reliable factors for predicting delirium in critically ill patients after cardiac surgery. The receiver operating characteristic curves and nomogram suggested a potential role for CD4+ T cells in mediating potential neuroinflammation of delirium.

Project description:Ankylosing spondylitis is a complicated consequence of genetic predisposition and environmental factors. Enthesitis is believed to be the hallmark of ankylosing spondylitis, and the chronic inflammatory state of this disease is perpetuated by the disturbances of both the innate immune system and the acquired immune system. To clarify the alteration of immune system in patients with AS, we conducted a meta-analysis concerning the proportions of major lymphocyte subsets in the peripheral blood of AS patients. We systematically searched PubMed and China National Knowledge Infrastructure (CNKI) for articles related to this subject. A total of 95 articles involving 4,020 AS patients and 3,065 healthy controls were included in the analysis. This meta-analysis is performed on R platform using R package "meta", and Egger's tests were used to determine the presence of publication bias. Results showed that the percentages of T cells, NK cells and NKT cells were not significantly different between AS patients and healthy controls, but B cells were significantly increased. Among the subsets of T cells, the proportions of CD4+ T cells, Th17 cells, Tfh cells as well as Th1/Th2 ratio were significantly increased, while Tregs were significantly decreased. Subgroup analysis showed that the proportions of Th17 among both PBMCs, T cells and CD4+ T cells were significantly elevated, while Tregs were only significantly lower in PBMCs. Subgroup analysis also demonstrated that Tregs defined by "CD4+CD25+FoxP3+", "CD4+CD25+CD127low"or "CD4+CD25+CD127-"were significantly downregulated, indicating that the selection of markers could be critical. Further study is warranted in order to elucidate the complicated interactions between different lymphocyte subsets in AS patients. This study implied that the disequilibrium between Th17 and Tregs, as well as between Th1 and Th2 could contribute to the pathogenesis of ankylosing spondylitis, further cementing the understanding that ankylosing spondylitis is a consequence of disrupted balance of innate immune system and acquired immune system.

Project description:BACKGROUND:Alterations in peripheral blood lymphocytes in cervical cancer have been reported, although conflicting views exist. The present study investigated the distributions of lymphocyte subsets in tumor tissue and peripheral blood samples from cervical cancer patients and precancerous lesion patients, and evaluated the correlations of lymphocyte subsets with clinicopathological and prognostic variables. METHODS:A total of 44 patients with stage IB1-IIA2 cervical cancer and 13 precancerous lesion patients were included. Lymphocytes were collected from the tumor tissue and the peripheral blood, and isolated by Lymphoprep density gradient centrifugation. The percentages of lymphocyte subsets were quantified by flow cytometry analysis, and the differences between lymphocyte subsets in the tumor tissue and peripheral blood were compared by SPSS. In addition, the relationships between lymphocyte subsets and clinicopathological and prognostic variables were analyzed. RESULTS:Our results revealed that the amount of total T lymphocytes, CD8+ T cells, granulocytes, pDCs, CD16+ monocytes and CD56high NK cells were significantly higher in the tumor tissue than in the peripheral blood in the cervical cancer patients, while those of CD4+ T cells, CD4+/CD8+ cell ratio, rdT cells, BDCA1+ mDCs, total monocytes, CD14+ monocytes, NK cells and CD56low NK cells exhibited the opposite trend (p < 0.05). The levels of total pDCs and BDCA1+ mDCs in the peripheral blood were significantly lower in the cervical cancer patients than in the precancerous lesion patients, while the proportion of CD16+ monocytes was elevated (p < 0.05). In addition, some lymphocyte subsets, especially CD4+ cells and CD8+ cells, and the CD4+/CD8+ cell ratio were closely associated with clinicopathological and prognostic parameters. CONCLUSIONS:These results suggested that distinct alterations in infiltrating lymphocyte subsets occurred in the tumor and were associated with clinicopathological and prognostic parameters. Systemic impairment of the immune system may occur in the antitumor response of cervical cancer patients.

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Aberrant alteration of peripheral B lymphocyte subsets in hepatocellular carcinoma patients.

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Aberrant alteration of peripheral B lymphocyte subsets in hepatocellular carcinoma patients.

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