1. Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer
- Author
-
Kyoung Ho Pyo, Hong In Yoon, Y. G. Kim, Jaehyung Jung, In-Ho Seo, Chun-Bong Synn, Su-Hyung Park, Soonmyung Paik, Yong Il Lee, Jeong-Eun Kwak, Yun Jeong Lee, Kyung Hwan Kim, Seongjin Choi, Hyo Sup Shim, Chang Gon Kim, Min Hee Hong, Hye Ryun Kim, Ellen Janine Kim, Beung-Chul Ahn, and Eui-Cheol Shin
- Subjects
0301 basic medicine ,Cancer Research ,Treatment response ,medicine.diagnostic_test ,Effector ,business.industry ,medicine.disease ,Flow cytometry ,Blockade ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,medicine ,Cancer research ,Biomarker (medicine) ,Lung cancer ,business ,CD8 - Abstract
Background The predictive value of immune monitoring with circulating CD8+ T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1+CD8+ T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. Methods Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8+ T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1+CD8+ T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). Results Circulating PD-1+CD8+ T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1+ cells among CD8+ T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8+ T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8+ T lymphocytes suppresses the effector functions of tumour antigen-specific CD8+ T lymphocytes. Conclusions Dynamic changes in circulating PD-1+CD8+ T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors.
- Published
- 2021