Analysis of T Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients.

Abstract

Purpose: As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).

Materials and methods: Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.

Results: The proportions of patients with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6% and 88.1%. A high cytotoxic T-cell (Tcyto) density was related to longer overall survival (OS). GC with a high ratio of Tcyto/total T-cells (Ttotal) and a low ratio of regulatory T-cells (Treg)/Ttotal showed better OS. A high density of PD-1- or TIM-3- expressing Tcyto were also associated with longer OS than a low density of those. Among memory T-cells (Tmem) subsets, GC with a high ratio of memory Tcyto/Tmem and a low ratio of memory Treg/Tmem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of Tcyto/Ttotal and memory Tcyto/Tmem.

Conclusion: T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1- or TIM-3 expressing T-cells were also associated with response to ICIs, while memory T-cells subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.