Weighting tumor-specific TCR repertoires as a classifier to stratify the immunotherapy delivery in non-small cell lung cancers.

Abstract

Analysis of T cell receptor (TCR) repertoires may contribute to better understanding of the response to immunotherapy. By deep sequencing of the TCR β chain complementarity-determining regions in the paired biopsies and peripheral blood specimens of 31 patients with non-small cell lung cancer (NSCLC) treated with anti-programmed death 1 (PD-1) or PD-ligand 1 (PD-L1) therapy, we developed a previously unidentified index, the TCR-based immunotherapy response index (TIR index), that estimated the degree of overlap of the TCR repertoire between tumor-infiltrating lymphocytes and circulating PD-1+CD8+T cells (shared TCR clones). This index correlated with response and survival outcomes of anti-PD-(L)1 treatment. All the TCR sequences of neoantigen-stimulated T cells were included in the shared TCR clones, indicating that TCR clones involved in TIR index estimation represented tumor-specific T cells. Therefore, the TIR index is a feasible approach for assessing tumor-specific TCR and stratifying patients with NSCLC for anti-PD-(L)1 therapy.

• Authors: Jiefei Han, Ruofei Yu, Jianchun Duan, Jin Li, Wei Zhao, Guoshuang Feng, Hua Bai, Yuqi Wang, Xue Zhang, Rui Wan, Jiachen Xu, Xin Wang, Yanfang Guan, Xuefeng Xia, Zhuoran Yao, Kailun Fei, David P Carbone, Zhijie Wang, Jie Wang
• Journal: Science advances (Sci Adv) Vol. 7 Issue 21 (05 2021) ISSN: 2375-2548 [Electronic] United States
• PMID: 34138742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Programmed Cell Death 1 Receptor
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Humans
• Immunotherapy
• Lung Neoplasms (genetics, therapy)
• Programmed Cell Death 1 Receptor (metabolism)
• Receptors, Antigen, T-Cell, alpha-beta