Chang Gon Kim1, Min Hee Hong2, Kyung Hwan Kim3, In-Ho Seo4, Beung-Chul Ahn2, Kyoung-Ho Pyo5, Chun-Bong Synn6, Hong In Yoon7, Hyo Sup Shim8, Yong Il Lee2, Seong Jin Choi4, Yun Jeong Lee4, Ellen Janine Kim9, Youngun Kim4, Jeong-Eun Kwak10, Jaehyung Jung10, Su-Hyung Park4, Soonmyung Paik6, Eui-Cheol Shin11, Hye Ryun Kim12. 1. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. 5. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; JE-UK Institute for Cancer Research, JEUK Co. Ltd., Gumi, Republic of Korea. 6. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. 7. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 8. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 9. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. 10. Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. 11. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: ecshin@kaist.ac.kr. 12. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: nobelg@yuhs.ac.
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.
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.
Authors: Reid W Merryman; Robert Redd; Erin Jeter; Jeff L Wong; Kristin McHugh; Carol Reynolds; Matthew Nazzaro; Aine Varden; Jennifer R Brown; Jennifer L Crombie; Matthew S Davids; David C Fisher; Eric Jacobsen; Caron A Jacobson; Austin I Kim; Ann S LaCasce; Samuel Y Ng; Oreofe O Odejide; Erin M Parry; Parastoo B Dahi; Yago Nieto; Robin M Joyce; Yi-Bin Chen; Alex F Herrera; Philippe Armand; Jerome Ritz Journal: Transplant Cell Ther Date: 2021-10-17
Authors: Patricia Mondelo-Macía; Ana María Rodríguez-Ces; María Mercedes Suárez-Cunqueiro; Laura Muinelo Romay Journal: Adv Exp Med Biol Date: 2022 Impact factor: 3.650