scholarly journals Association of Lymphocyte Subsets in Advanced Non-Small Cell Lung Cancer Patients with the Efficacy and Prognosis of Immune Checkpoint Inhibitor Therapy: A Retrospective Study

Author(s):  
Yi Yan ◽  
Junmei Jia

Abstract Background The adaptation of immune checkpoint inhibitors (ICIs) has achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore some biomarkers to predict the efficacy and survival rate of patients with advanced NSCLC after immunotherapy. The objective of this study is to monitor the changes of peripheral blood lymphocyte subpopulations and analyze their correlation with the efficacy and prognosis of immunotherapy. Methods A total of 153 patients with advanced NSCLC were examined. Peripheral blood lymphocyte subsets including CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells, and Tregs were collected before any treatment, before immunotherapy, and after 4 cycles of immunotherapy. T-test was used to analyze the influencing factors of lymphocyte subtypes and their changes before and after immunotherapy. Logistic regression was used to analyze the relationship between lymphocyte subtypes and efficacy with ROC curve being plotted. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subtypes and progression-free survival (PFS). Results Gender, age, pathology, distant metastasis, and EGFR mutations all affect the proportion of peripheral blood lymphocyte subpopulations in patients with advanced NSCLC. Compared with baseline, the effective group showed that the proportions of CD4+ T cells, CD4+/CD8+ ratio, NK cells and Tregs were significantly higher, and the proportions of CD8+ T cells were significantly lower in peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group showed no signs of significant differences. Baseline CD4+ T cells, NK cells and Tregs were independent predictors of immunotherapy efficacy and PFS. Conclusions Immune checkpoint inhibitors induce changes in the proportion of peripheral blood lymphocyte subsets in patients with effective immunotherapy. The levels of lymphocyte subsets have a good predictive value for efficacy and prognosis of patients with advanced NSCLC.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2387-2387 ◽  
Author(s):  
Geoffrey L. Uy ◽  
Matthew S. Holt ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
...  

Abstract Bortezomib (VELCADE®) is a potent inhibitor of the proteasome which exerts its antimyeloma effect in part by blocking the activation of NF-κB. As NF-κB is critical for lymphocyte development and survival, there is great interest in harnessing the potential immunomodulatory effects of bortezomib. In murine hematopoietic transplantation models, bortezomib inhibits in vitro mixed lymphocyte responses and promotes the apoptosis of alloreactive T cells protecting against acute graft-versus-host disease. However, no data exists on the in vivo effects of bortezomib on human T cells. To characterize the effects of bortezomib on immune function, we profiled peripheral blood lymphocytes subsets and T cell associated cytokines in 39 patients with multiple myeloma. Two cycles of bortezomib 1.3 mg/m2 were administered by intravenous infusion on days 1, 4, 8, and 11 of a 21-day treatment cycle. The patients had received prior induction chemotherapy and would proceed to autologous transplant following treatment with bortezomib. Study population consists of 23 male and 16 female patients with the median age of 56 years (range 38–69). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (28), IgA (10), light chain only (1), with stage I (1), II (12), or stage III (26) disease. Peripheral blood was collected at baseline (cycle 1, day 1) and at one week after the last dose of bortezomib (cycle 2, day 18) and analyzed for lymphocyte subsets by standard multicolor flow cytometry. Th1 and Th2 serum cytokines were measured at the same timepoints using a multiplexed cytometric bead array (BD Biosciences). Following treatment with bortezomib, no significant changes were detected in either Th1 or Th2 serum cytokine levels: IL-2 (p=0.116), TNF-alpha (p=0.854), IFN-gamma (p=0.070), IL-4 (p=0.240), IL-6 (0.236), IL-10 (0.151) as analyzed by Wilcoxon signed ranks test. Analysis of lymphocyte subsets using a paired student’s T-test demonstrated a 38% decrease in CD56+ NK cells (p=0.02) and a 26% increase in CD4/CD8 ratio (p=0.0006) which appears to be secondary to a decrease in CD8+ cytotoxic T-cells (p=0.054). (Table 1.) In conclusion, we observe an alteration of lymphocyte subsets following only two cycles of bortezomib. Further analysis of the effects of long term treatment with bortezomib is warranted. These studies may provide insights into the role of bortezomib as an immunomodulatory agent. Peripheral Blood Lymphocyte Subsets Pre-bortezomib (/mm 3 ) Post-bortezomib(/mm 3 ) Difference(/mm 3 ) P-value CD2 1446 1259 −187 0.085 CD3 1273 1160 −113 0.28 CD4 842 802 −40 0.54 CD8 412 337 −75 0.055 CD19 90 94 4 0.86 CD20 87 95 8 0.78 CD56 206 148 −58 0.022 CD4/CD8 ratio 2.53 3.19 0.66 0.0006


2018 ◽  
Vol 32 ◽  
pp. 205873841879231 ◽  
Author(s):  
Antonella Frattari ◽  
Ennio Polilli ◽  
Vanessa Primiterra ◽  
Vincenzo Savini ◽  
Tamara Ursini ◽  
...  

A better knowledge of factors predicting the development of sepsis in patients hospitalized in intensive care unit (ICU) might help deploy more targeted preventive and therapeutic strategies. In addition to the known clinical and demographic predictors of septic syndromes, in this study, we investigated whether measuring T and B lymphocyte subsets upon admission in the ICU may help individualize the prediction of ensuing sepsis during ICU stay. Between May 2015 and December 2016, we performed a prospective cohort study evaluating peripheral blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 + (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on blood samples collected 2 days after admission in the ICU. We enrolled 176 patients, 65.3% males, with mean age of 61.1 ± 15.4 years. At univariate analyses, higher percentages of CD19 B-cells were significantly associated with ensuing sepsis (20.5% (15.7–27.7)% vs 16.9% (11.3–22)%, P = 0.0001), whereas median interquartile range (IQR) proportions of CD4 T-cells (41.2% (33.4–50.6)% vs 40% (35–47)%, P = 0.5), CD8 T-cells (21.1% (15.8–28.2)% vs 19.6% (14.6–25.1)%, P = 0.2) and CD56 T-cells (1.7% (0.9–3.1)% vs 1.45% (0.7–2.3)%, P = 0.4) did not reveal any significant association. An unexpected, highly significant inverse correlation of CD8 T-cells and CD19 B-cells proportions, however, was observed, suggesting that patients with lower CD19 and higher CD8 proportions might be somehow protected from ensuing sepsis. We therefore studied the ability of the CD8/CD19 ratio to predict ensuing sepsis in our sample. In final models of multivariate logistic regression, the following independent associations were found: previous antibiotic exposure (odds ratio (OR): 3.8 (95% confidence interval (CI): 1.35–10.87), P = 0.01), isolation of at least one multi-drug resistant organism at any time during ICU stay (OR: 8.4 (95% CI: 3.47–20.6), P < 0.0001), decreasing age (OR: 0.9 (95% CI: 0.93–0.99), P = 0.02) and a CD8/CD19 ratio >2.2 (OR: 10.3 (95% CI: 1.91–55.36), P = 0.007). Our data provide preliminary evidence that immune characterization of critically ill patients on ICU admission may help personalize the prediction of ensuing sepsis during their ICU stay. Further polycentric evaluation of the true potential of this new tool is warranted.


1995 ◽  
Vol 14 (1) ◽  
pp. 62-67 ◽  
Author(s):  
A. Uddhammar ◽  
G. Roos ◽  
B. Näsman ◽  
S. Rantapää Dahlqvist

2015 ◽  
Vol 13 (1) ◽  
pp. 30 ◽  
Author(s):  
Noriko Tada ◽  
Kazushige Kawai ◽  
Nelson H Tsuno ◽  
Soichiro Ishihara ◽  
Hironori Yamaguchi ◽  
...  

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