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

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 p...

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Published in:European journal of cancer (1990) 2021-01, Vol.143, p.113-126
Main Authors: Kim, Chang Gon, Hong, Min Hee, Kim, Kyung Hwan, Seo, In-Ho, Ahn, Beung-Chul, Pyo, Kyoung-Ho, Synn, Chun-Bong, Yoon, Hong In, Shim, Hyo Sup, Lee, Yong Il, Choi, Seong Jin, Lee, Yun Jeong, Kim, Ellen Janine, Kim, Youngun, Kwak, Jeong-Eun, Jung, Jaehyung, Park, Su-Hyung, Paik, Soonmyung, Shin, Eui-Cheol, Kim, Hye Ryun
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Anti-programmed cell death-1 treatment
Antigens
Apoptosis
Biomarker
Carcinoma, Non-Small-Cell Lung - drug therapy
CD8 antigen
CD8+ T lymphocytes
CD8-Positive T-Lymphocytes - metabolism
Cell death
Female
Flow cytometry
Humans
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Inhibitors
Lung cancer
Lung Neoplasms - drug therapy
Lymphocytes
Lymphocytes T
Male
Memory cells
Metastases
Middle Aged
Non-small cell lung carcinoma
Non-small-cell lung cancer
Patients
PD-1 protein
Peripheral blood
Phenotyping
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Small cell lung carcinoma
Subgroups
Survival
Tumors
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Summary: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. 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). 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. 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. •Current biomarkers for PD-1 blockade are suboptimal and require invasive procedures.•Reduction of PD-1+ cells in CD8+ T lymphocytes predicts favourable treatment outcomes.•Suppressive function of circulating PD-1+CD8+ T lymphocytes was uncovered.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2020.10.028