Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer

Degree of expression of programmed death-ligand 1 (PD-L1) is related with Immune check point inhibitors (ICIs) response but it needs sufficient tumor tissue. There is unmet need for easily accessible and prognostic peripheral blood (PB) biomarkers. We investigated the application of serum peripheral lymphocyte count (PLC) as a predictive PB biomarker for ICI response in patients with NSCLC. We conducted a retrospective study and reviewed the patients with NSCLC who were treated with ICIs from April 1, 2016, to March 31, 2019. The PLC before and after 1 month of immunotherapy was collected. We evaluated the association between PLC and progression-free survival (PFS), overall survival (OS) and adverse events. A total of 231 patients were treated with ICIs for NSCLC. The median follow-up period was 4.7 months and the disease progressed in 138 patients (59.7%). Compared with the lowest quartile (Q1: the lowest 25%), the highest quartile (Q4: the highest 25%) of post-treatment PLC showed a significantly higher PFS (HR 0.28, 95% CI 0.16–0.52) and OS (HR 0.35, 95% CI 0.19–0.65) in the adjusted model. An association between adverse events and PLC was not observed. We revealed that an increased pre- and post-treatment PLC was associated with favorable PFS and OS with NSCLC patients treated with ICIs. PLC could be a helpful for ICI responses in NSCLC.

Features of CD-­­phenotype of peripheral blood lymphocytes in adult patients with atopic dermatitis during the exacerbation

Objective — to study the dynamics of peripheral blood lymphocytic populations in adult patients with atopic dermatitis (AD) with the onset of the disease in childhood, depending on the level of IgE secretion and the method of treatment. Materials and methods. We examined 67 adult patients with AD, which were divided into 4 groups depending on the level of total serum IgE and the basic treatment or treatment in combination with Glycine and Ketotifen. The severity of AD was determined by the SCORAD index. The content of peripheral blood lymphocytes according to the phenotype CD3+, CD4+, CD8+, CD19+, CD65+, HLADR+ and CD95+ was assessed during hospitalization of patients, at the end of the inpatient stage of treatment and after 1 month of outpatient follow-up. The obtained data were compared with the indices of the control group and between the groups of examined patients with AD in the dynamics of their treatment and observation. The results were processed statistically using the methods of parametric and nonparametric statistics. Results and discussion. The indices of the number of cells of peripheral lymphocytic populations of different CD pheno­type in the groups in the dynamics of observation were determined, their relationship with the severity of the course of AD was established, and differences were found depending on the pathogenetic variant of AD. Against the background of an exacerbation of AD, a significant increase in the number of cells in most of the defined populations was revealed, with its gradual decrease as the clinical manifestations of AD subsided. It was established that 1 month after achievement of clinical/subclinical remission, a part of the peripheral blood lymphocytic populations was characterized by higher values compared to the norm. In patients with an IgE-dependent AD variant, aggravation is accompanied by high levels of peripheral lymphocytes with CD3+, CD4+, CD8+, CD19+ and HLA-DR phenotypes, which more often than in the case of an IgE-independent variant of AD, remain above the norm after 1 month of outpatient monitoring. Introduction of glycine and ketotifen to the treatment complex for patients with AD is accompanied by a faster return of peripheral lymphocyte cells to normal values, which is more evident in patients with an IgE-dependent variant of AD. Conclusions. In adult AD patients, the dynamics of the number of peripheral lymphocyte population cells depends on the severity of the disease, its pathogenetic variant and the treatment received by the patient. Against the background of the use of glycine and ketotifen, the normalization of indicators of peripheral lymphocytic populations occurs significantly faster than with only standard basic therapy.

Lymphocyte subsets in the peripheral blood are disturbed in systemic sclerosis patients and can be changed by immunosuppressive medication

Systemic sclerosis (SSc) is a severe chronic disease with a broad spectrum of clinical manifestations. SSc displays disturbed lymphocyte homeostasis. Immunosuppressive medications targeting T or B cells can improve disease manifestations. SSc clinical manifestations and immunosuppressive medication in itself can cause changes in lymphocyte subsets. The aim of this study was to investigate peripheral lymphocyte homeostasis in SSc with regards to the immunosuppression and to major organ involvement. 44 SSc patients and 19 healthy donors (HD) were included. Immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting was performed. Cytokine secretions of stimulated B cell cultures were measured. SSc patients without immunosuppression compared to HD displayed lower γδ T cells, lower T helper cells (CD3+/CD4+), lower transitional B cells (CD19+/CD38++/CD10+/IgD+), lower pre-switched memory B cells (CD19+/CD27+/IgD+), and lower post-switched memory B cells (CD19+/CD27+/IgD−). There was no difference in the cytokine production of whole B cell cultures between SSc and HD. Within the SSc cohort, mycophenolate intake was associated with lower T helper cells and lower NK cells (CD56+/CD3−). The described differences in peripheral lymphocyte subsets between SSc and HD generate further insight in SSc pathogenesis. Lymphocyte changes under effective immunosuppression indicate how lymphocyte homeostasis in SSc might be restored.

Immunity Profiling of COVID-19 Infection, Dynamic Variations of Lymphocyte Subsets, a Comparative Analysis on Four Different Groups

Background: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. Methods: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive–positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative–positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or “COVID-like” group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative–affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn’t show ground-glass opacities). Finally, the negative–negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. Results: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. Conclusions: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy.

Changes in peripheral lymphocyte populations in patients with advanced/recurrent ovarian cancer undergoing splenectomy during cytoreductive surgery

Background To investigate changes in peripheral lymphocyte subsets after splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancers. Methods We enrolled 83 patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery. Twenty patients who also underwent splenectomy were assigned to the splenectomy cohort and the rest were assigned to the non-splenectomy cohort. Flow cytometry was used to measure peripheral lymphocyte subsets consisting of T cells, regulatory T cells, natural killer cells, B cells, and activation antigens before and after surgery. Results There was no difference in the number and distribution of peripheral lymphocyte subsets between the two cohorts before surgery. After surgery, we observed elevated levels of T cells (CD3+, CD3+CD8+) in the splenectomy cohort compared to those in the non-splenectomy cohort, and the difference was statistically significant. CD8+CD28+ T cells had a significant decreasing tendency (P = 0.011) while CD3+/HLA-DR+ T cells showed the opposite trend (P = 0.001) in the splenectomy cohort. The proportion of Tregs (P = 0.005) and B cells (P < 0.001) including CD3−/HLA-DR+ B cells (P = 0.007) increased after surgery, and the absolute number of T cells and NK cells decreased to different extents (P < 0.001) in the non-splenectomy cohort. The post-operative percentage of CD8+CD28+ T cells was less than the pre-operative percentage (P = 0.022), which was similar to the splenectomy cohort. There was no significant difference in progression-free survival or overall survival between the groups after a median follow-up time of 41 months. Conclusions The changes in peripheral lymphocyte populations were different between patients with and those without splenectomy during cytoreductive surgery for ovarian cancers. T cells were increased and activated in the splenectomy cohort, whereas, B cells were increased and activated in the non-splenectomy cohort.

Characteristics of Peripheral Lymphocyte Subsets in Patients With Acute-On-Chronic Liver Failure Associated With Hepatitis B

Background and Aims: Acute-on-chronic liver failure (ACLF) is a rare, but dramatic clinical syndrome. There is substantial evidence suggesting that immunity-mediated inflammation plays an important role in HBV-ACLF. Our aim was to characterize the proportion and cell counts of peripheral blood lymphocyte subsets in acute-on-chronic liver failure patients caused by HBV infection.Methods: One hundred and seventeen patients were enrolled in this study, including those with HBV-related ACLF (HBV-ACLF; n = 70), and HBV related non-ACLF patients (HBV non-ACLF; n = 47). Demographics, clinical and laboratory data at hospital admission were retrospectively analyzed. The percentage and cell count of peripheral lymphocyte subsets were evaluated by flow cytometry. Comparison analysis was performed by t-test or non-parametric Mann–Whitney U-test. Actuarial probabilities of death were calculated by the Kaplan-Meier method.Results: Both circulating lymphocyte count and lymphocyte percentage were significantly reduced in patients with HBV-ACLF (P &lt; 0.001). The CD8+ T cell, CD4+ T cell, and CD16+CD56+ NK cell counts were significantly decreased in HBV-ACLF. Consistently, flow cytometric analysis showed that CD8+ T cell counts were significantly decreased in non-survivors, while no significant differences were found in CD4+ T cell, CD19+ B cell, or CD56+CD16+ NK cell counts. Furthermore, the group with the lower CD8+ T cell count displayed a significantly higher mortality rate compared with the group with the higher CD8+ T cell count.Conclusions: The abnormal prevalence of lymphocyte subsets may be important in the pathogenesis of HBV-ACLF. The decrease in CD8+ T cell counts may be related to poor survival in HBV-ACLF patients.

Evaluation of lymphocyte subtypes in COVID-19 patients

Background: Although the many aspects of COVID-19 have not been yet recognized, it seems that the dysregulation of the immune system has a very important role in the progression of the disease. In this study the lymphocyte subsets were evaluated in COVID-19 patients with different severity. Methods: In this prospective study, the levels of peripheral lymphocyte subsets (CD3+, CD4+, CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were measured in 67 confirmed patients with COVID-19 on the first day of admission. Results: The mean age of cases was 51.3 plus-or-minus sign 14.8 years. Thirty-two patients (47.8%) were classified as severe cases and 11 (16.4%) patients were categorized as critical. The frequency of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells; and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, CD16+56+ lymphocytes were lower in more severe cases in comparison to milder cases. Percentages of lymphocytes, T cells, and NK cells were significantly lower inthe patients who died (p= 0.002 and P= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study suggests that the frequency of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells were difference in the severe COVID-19 patients. Moreover, lower frequency of , T cells, and NK cells are predictors of mortality of these patients.

Peripheral Lymphocyte Count as a Surrogate Marker of Immune Checkpoint Inhibitor Therapy Outcomes in Patients with Non-Small-Cell Lung Cancer

BackgroundDegree of expression of programmed death-ligand 1 (PD-L1) is related with Immune check point inhibitors (ICIs) response but is not obligate predictive marker and needs sufficient tissue. Therefore, there is unmet need for easily accessible peripheral blood (PB) biomarkers and evaluation of the prognostic value of this marker is needed. We investigated the application of serum peripheral lymphocyte count (PLC) as a predictive PB biomarker for ICI response in patients with NSCLC. MethodsWe conducted a retrospective study and reviewed the medical charts of patients with NSCLC who were treated with ICIs at Seoul National University Hospital. We evaluated the association between PLC and progression-free survival using a Cox proportional hazard model. The PLC before and after 1 month of immunotherapy was collected. The quartile groups of PLC were compared using the Kruskal-Wallis statistical test.ResultsA total of 231 patients were treated with immunotherapy for NSCLC. The median follow-up period was 4.7 months. During the follow-up period, the disease progressed in 138 patients (59.7%). The post-treatment PLC groups Q2-4 showed significantly lower disease progression than group Q1 in our adjusted model (Q4 hazard ratio: 0.41, 95% confidence interval: 0.25–0.68, p < 0.001). The overall survival also showed similar results. An association between adverse events and PLC was not observed in this study. ConclusionWe revealed that an increased post-treatment PLC was associated with favorable progression-free and overall survival with NSCLC patients treated with ICIs. Therefore, PLC could be a surrogate marker for ICI responses in NSCLC.