Soluble immune-checkpoint factors: a potential immunotherapy biomarker

Abstract

There is unmet need for additional biomarkers to better select patients with non-small cell lung cancer (NSCLC) that are likely to benefit from immunotherapy in order to improve patient outcomes, reduce patient toxicity, and relieve the growing burden of healthcare costs. In this issue of the JCI, Hayashi and colleagues evaluated soluble forms of the immune checkpoint molecules PD-L1, PD-1, and CTLA-4 in the plasma of patients with advanced NSCLC who had been treated with anti-PD-1/L1 therapy. The findings suggest that these soluble immune-checkpoint factors may provide a complementary biomarker to PD-L1 IHC, although application into the clinic may not be straightforward.

Figure 1. Tissue analysis to determine the success of immunotherapeutic intervention may require multiple analyses.

Determining whether immunotherapeutic intervention administered to NSCLC patients will be successful may require multiple analyses on different tissue specimens. (i) Tumor samples may be tested via microfluidic assays that detect splicing variants of immune checkpoint proteins produced by tumor cells and immune cells such as dendritic or T cells (7). (ii) Soluble checkpoint proteins can be detected in the plasma of patients (4). (iii) Tumor specimens may be assessed histologically for immune checkpoint proteins.