Predictable Roles of Peripheral IgM Memory B Cells for the Responses to Anti-PD-1 Monotherapy Against Advanced Non-Small Cell Lung Cancer.

Liliang Xia,Weimin Xia,Shun Zhang,Wenfeng Li,Yaxian Yao,Jin Kang,Ying Wang,Limin Guo,Shun Lu,Ziming Li,Yuer Gao,Hongyan Chen,Yi Yang,Ruiming Sun,Jinji Yang

doi:10.3389/fimmu.2021.759217

Abstract

Tumor-infiltrating B cells and tertiary lymphoid structures have been identified to predict the responses to immune checkpoint inhibitors (ICIs) in cancer immunotherapy. Considering the feasibility of sample collection, whether peripheral B cell signatures are associated with the responses to ICI therapy remains unclear. Herein, we have defined peripheral B cell signatures in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1 monotherapy and investigated their associations with clinical efficacy. It was found that the percentages of B cells before the treatment (baseline) were significantly higher (P = 0.004) in responder (R, n = 17) than those in non-responder (NonR, n = 33) NSCLC patients in a discovery cohort. Moreover, the percentages of baseline IgM+ memory B cells were higher (P < 0.001) in R group than those in NonR group, and associated with a longer progression free survival (PFS) (P = 0.003). By logistic regression analysis peripheral baseline IgM+ memory B cells were identified as an independent prognostic factor (P = 0.002) for the prediction of the responses to anti-PD-1 monotherapy with the AUC value of 0.791, which was further validated in another anti-PD-1 monotherapy cohort (P = 0.011, n = 70) whereas no significance was observed in patients receiving anti-PD-L1 monotherapy (P = 0.135, n = 30). Therefore, our data suggest the roles of peripheral IgM+ memory B cells in predicting the responses to anti-PD-1 treatment in Chinese advanced NSCLC patients.

Highlights

Immune checkpoint inhibitors (ICIs) targeting programmed cell death1 (PD1) and its ligand (PD-L1) have greatly improved therapeutic outcomes in multiple carcinomas including advanced non-small cell lung cancer (NSCLC)
A total of 120 advanced NSCLC patients receiving anti-progression diseases (PD)-1 monotherapy and 30 patients receiving anti-PD-L1 monotherapy were recruited in this study (Table 1)
Among those receiving antiPD-1 monotherapy, 50 patients with nivolumab monotherapy were designated as a discovery cohort and another 70 patients were as a validation cohort

Summary

Introduction

Immune checkpoint inhibitors (ICIs) targeting programmed cell death (PD1) and its ligand (PD-L1) have greatly improved therapeutic outcomes in multiple carcinomas including advanced non-small cell lung cancer (NSCLC). PD-L1 expression on tumor cells has been used in clinic as an indicative biomarker [1]. Due to the difficulties in the collection of tumor biopsies from cancer patients and insufficient biomarkers to identify benefit patients, it is still necessary to investigate novel indicators associated with the responses to ICI treatment. Several peripheral CD8+ T cell signatures have been reported to be associated with clinical outcomes of anti-PD-1/PD-L1 immunotherapy [8, 10]. B cells and tertiary lymphoid structures (TLSs) in the tumor microenvironment (TME) are identified to promote the responses to ICI treatment, illustrating the significance of B cells in anti-PD-1/PD-L1 immunotherapy [12,13,14]. Whether systematic B cell signatures are associated with the responses to ICI therapy needs to be further explored

Methods

Results

Conclusion