Open AccessWeighting tumor-specific TCR repertoires as a classifier to stratify the immunotherapy delivery in non–small cell lung cancers
Author(s) -
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
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abd6971
Subject(s) - t cell receptor , immunotherapy , cd8 , immunology , biology , lung cancer , t cell , cancer research , immune system , medicine , oncology
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.