Abstract 3189: Dynamics characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire during immune checkpoint blockade in cancer
Authors: Li Ye , Wang Jiaqian , Sun Shengjie , Wu Liangliang , Zhang YunXiao , Zhang Guoqing , Li Xiaoting , Jiao Shunchang 
Published: September 2020

Introduction: Immune checkpoint blockade (ICB) targeted to CTLA-4, PD-1, and PD-L1 can promote anti-tumor T cell immunity and clinical responses. Tracking the dynamic changes of the T Cell Repertoire (TCR) can reflect the evolution of the immune system in tumor immunotherapy patients, predict the immune response to ICB, and provide high-value information for clinical monitoring of immune function status of cancer patients to make effective clinical decisions. The purpose of this study was to explore the correlation between the peripheral blood TCR repertoire dynamic changes and the immune response of patients with anti-PD-1/PD-L1, and to accurately guide the individualized treatment of immunotherapy.

Methods: To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 31 advanced solid tumors (most were non-small cell lung cancer) patients treated with immune checkpoint blockade. The blood samples were obtained at baseline of treatment with PD-1/PD-L1 antibody, one to two additional blood samples were obtained during treatment to assess dynamic changes. Shannon-Wiener index was used to identify the diversity of TCR receptor. D50 index was used to account for diversity from the cumulative 50% of the total CDR3s counted in the sample.

Results:Shannon-Wiener index at baseline was higher in durable clinical benefit (CB) group than non-clinical benefit (NCB) group (p value = 0.0040) treated with anti-PD1/PD-L1, and significantly increased in CB group ( p value = 0.031). There is a significant correlation between D50 index and clinical benefit during treatment (p value = 0.025). The higher the D50 index, the more likely it is to have durable clinical benefit. Significant difference in progression-free survival (PFS) rate was identified between the D50 high and D50 low groups (p value = 0.037). We validated this result in an independent cohort of NSCLC patients treated with anti-PD1/PD-L1(N=12).

Conclusions:This study revealed the dynamic changes of peripheral blood T cell receptor beta-chain repertoire in patients with solid tumors before and during anti-PD1/PD-L1 treatment. This study found that baseline TCR diversity was associated with clinical efficacy. Patients with durable clinical benefit had an increased overall diversity of TCR. The D50 index of the sample during treatment can reflect whether the patient could benefit from anti-PD1/PD-L1 treatment or not, and was a significant prognostic factor for progression-free (PFS). These analyses provide that the peripheral blood TCR repertoire parameters may be useful for prognosis prediction and rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors.

Citation Format: Ye Li, Jiaqian Wang, Shengjie Sun, Liangliang Wu, YunXiao Zhang, Guoqing Zhang, Xiaoting Li, Shunchang Jiao. Dynamics characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire during immune checkpoint blockade in cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3189.