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Dynamics of Circulating Immune Cells During Chemoradiotherapy in Patients with Non-Small Cell Lung Cancer Support Earlier Administration of Anti-PD-1/PD-L1 Therapy

Authors
 Kyung Hwan Kim  ;  Hongryull Pyo  ;  Hoyoung Lee  ;  Dongryul Oh  ;  Jae Myoung Noh  ;  Yong Chan Ahn  ;  Hong In Yoon  ;  Hyowon Moon  ;  Jiyun Lee  ;  Sehhoon Park  ;  Hyun-Ae Jung  ;  Jong-Mu Sun  ;  Se-Hoon Lee  ;  Jin Seok Ahn  ;  Keunchil Park  ;  Bo Mi Ku  ;  Myung-Ju Ahn  ;  Eui-Cheol Shin 
Citation
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol.113(2) : 415-425, 2022-06 
Journal Title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN
 0360-3016 
Issue Date
2022-06
MeSH
B7-H1 Antigen / therapeutic use ; CD8-Positive T-Lymphocytes ; Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy / methods ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms* ; Lymphocytes, Tumor-Infiltrating ; Programmed Cell Death 1 Receptor
Abstract
Purpose: Chemoradiotherapy (CRT) followed by consolidation immune checkpoint inhibitors significantly improves survival in unresectable locally advanced non-small cell lung cancer. However, the optimal sequence for CRT and immune checkpoint inhibitors has not yet been established. We investigated the dynamics of peripheral blood immune cells during CRT to determine the best sequence for treatment.

Methods and materials: Peripheral blood samples were prospectively collected pretreatment, weekly during CRT for 6 weeks, and 1 month posttreatment in 24 patients with locally advanced non-small cell lung cancer who received definitive CRT. Immune cell analysis was performed by flow cytometry. Ex vivo PD-1 blockade assays were performed by IFN-γ intracellular cytokine staining.

Results: Lymphopenia was prominently observed during CRT and mostly recovered 1 month post-CRT. Robust proliferation of CD8+ T cells was induced, peaking in the last week during CRT and decreasing post-CRT. The robust proliferation of CD8+ T cells led to an increase in the frequency of CD28-CD57+ replicative senescent and terminally differentiated cells post-CRT. Tumor-reactive CD8+ T cells increased during CRT and peaked in the last week. One month post-CRT, the frequency of tumor-reactive CD8+ T cells decreased and TOXhiTCF1lo terminally exhausted CD8+ T cells significantly increased. Anti-PD-1-induced functional restoration of PD-1+CD8+ T cells was maximized in the last week of CRT and significantly decreased post-CRT.

Conclusions: The findings suggest that earlier administration of PD-1 blockade may be associated with superior efficacy compared with delayed administration after completion of CRT. These findings provide an immunologic rationale for optimal timing of combining immune checkpoint inhibitors with CRT in clinical trials.
Full Text
https://www.sciencedirect.com/science/article/pii/S0360301622001432?via%3Dihub
DOI
10.1016/j.ijrobp.2022.02.003
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191562
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