Abstract 1192: Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients
Authors: Shirasawa Masayuki , Yoshida Tatsuya , Takeyasu Yuki , Matsutani Takaji , Yagishita Shigehiro , Kitano Shigehisa , Kuroda Hiroaki , Hida Toyoaki , Kurata Takayasu , Ohe Yuichiro 
Published: March 2024

Background: Chemoradiotherapy (CRT) followed by Durvalumab consolidation has been the standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients. This study aimed to evaluate how CRT changes TCR repertoire on peripheral CD8+PD-1+ T-cells, and the change affects the clinical outcomes of CRT followed by durvalumab treatment.

Methods: This was a prospective cohort study conducted from November 2019 to May 2021 in three institutes (National Cancer Center Hospital, Kansai Medical University Hospital, and Aichi Cancer Center Hospital) in Japan. We revealed the diversity of TCR repertoire (diversity evenness 50 [DE50]) on PD-1+CD8+ T cells, and CD8+ T cell phenotype in PBMCs before and after CRT treatment.

Results: A total of 40 patients treated with CRT were included. Of these patients, 32 patients received durvalumab consolidation treatment after CRT (Durva cohort). The diversity and usage of T cell Receptor Beta Variable (TRBV) and T-cell receptor beta joining gene (TRBJ) usage were significantly positively correlated before and after CRT (TRBV usage: r=0.62, p&lt;0.001, TRBJ usage: r=0.55, p&lt;0.001). Regarding the association of TCR repertoire diversity with CD8+ T cell phenotype, DE50 and frequencies of CD8 naive were significantly positively correlated before CRT (p=0.049), while there was no correlation between PD-L1 expression and TCR repertoire before CRT (r=0.03, p=0.89) In Durva cohort, DE50 in patients with non-recurrence was higher than those with recurrence both before and after CRT (Before CRT: 0.0032 vs. 0.0019, p=0.13, After CRT: 0.0026 vs. 0.0014, p=0.06). The progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than those with DE50Low (NR vs. 14.3 months; p=0.01). Moreover, when the patients were exploratory classified based on the PD-L1 expression status and the diversity of TCR repertoire, the PFS of the CRT followed by durvalumab apparently differed (DE50High, PD-L1 TPS≥1%, NR, and DE50Low, PD-L1 TPS&lt;1%, 5.9 (4.6-7.3) months, p=0.001).

Conclusions: TCR diversity of peripheral CD8+PD-1+ T-cell predicted the recurrence in unresectable locally advanced NSCLC patients treated with chemoradiotherapy followed by durvalumab maintenance. Additionally, the TCR diversity combined with PD-L1 expression status could more accurately predict the efficacy of the CRT followed by durvalumab.

Citation Format: Masayuki Shirasawa, Tatsuya Yoshida, Yuki Takeyasu, Takaji Matsutani, Shigehiro Yagishita, Shigehisa Kitano, Hiroaki Kuroda, Toyoaki Hida, Takayasu Kurata, Yuichiro Ohe. Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1192.