The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors.

Min Wang,Xiaoyang Zhai,Yuying Li,Jingyuan Guan,Ji Li,Shuhui Xu,Hui Zhu

doi:10.3389/fimmu.2021.670391

Abstract

Recently, the overall survival (OS) and progression-free survival (PFS) of patients with advanced cancer has been significantly improved due to the application of immune checkpoint inhibitors (ICIs). Low response rate and high occurrence of immune-related adverse events (irAEs) make urgently need for ideal predictive biomarkers to identity efficient population and guide treatment strategies. Cytokines are small soluble proteins with a wide range of biological activity that are secreted by activated immune cells or tumor cells and act as a bridge between innate immunity, infection, inflammation and cancer. Cytokines can be detected in peripheral blood and suitable for dynamic detection. During the era of ICIs, many studies investigated the role of cytokines in prediction of the efficiency and toxicity of ICIs. Herein, we review the relevant studies on TNF-α, IFN-γ, IL-6, IL-8, TGF-β and other cytokines as biomarkers for predicting ICI-related reactions and adverse events, and explore the immunomodulatory mechanisms. Finally, the most important purpose of this review is to help identify predictors of ICI to screen patients who are most likely to benefit from immunotherapy.

Highlights

Immune checkpoint inhibitors (ICIs) therapy has shown improved clinical responses and significant survival benefits in patients with locally advanced or advanced solid tumor types
Boutsikou et al [21] reported increased tumor necrosis factor (TNF)-a levels at the time before and 3 months after anti-programmed cell death 1 (PD-1) was correlated with improved response and prolonged survival (P=0.009) in 26 non-small cell lung cancer (NSCLC) patients treated with progressive disease (PD)-1 inhibitors, while not association with progression-free survival (PFS)
Results increased levels of IL-6 associate with psoriasiform dermatitis increased levels of IL-6 associate with psoriasiform dermatitis increased IL-6 level correlate with SAE rate low baseline IL-6, IL-8, and sCD25 associate with colitis low baseline IL-6 level act as independent predicted factor family kinases JAK1 and JAK2

Summary

INTRODUCTION

Immune checkpoint inhibitors (ICIs) therapy has shown improved clinical responses and significant survival benefits in patients with locally advanced or advanced solid tumor types. We retrospect the potential value of cytokines in predicting the efficacy and adverse reactions of immune checkpoint therapy (ICT) and intends to identify patients who will benefit from ICIs. Tumor necrosis factor (TNF) was named in 1975 by Carswell because TNF caused tumor bleeding and necrosis [33]. Boutsikou et al [21] reported increased TNF-a levels at the time before and 3 months after anti-PD-1 was correlated with improved response and prolonged survival (P=0.009) in 26 NSCLC patients treated with PD-1 inhibitors, while not association with PFS. IFN-g binds to the cell surface receptors and triggers phosphorylation of JANUS

Results

26 NCSLC PD-1

CONCLUSION