Eun-Ah Choe1, Yoon Jin Cha2, Jae-Hwan Kim3, Kyoung Ho Pyo4, Min Hee Hong5, Seong Yong Park6, Hyo Sup Shim7, Inkyung Jung8, Chang Young Lee9, Byoung Chul Cho10, Hye Ryun Kim11. 1. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: eunahchoe@yuhs.ac. 2. Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: YOONCHA@yuhs.ac. 3. JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea. Electronic address: KIMJW7@yuhs.ac. 4. JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea. Electronic address: pkhpsh@gmail.com. 5. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: MINHEE_HONG@yuhs.ac. 6. Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: SYPARKCS@yuhs.ac. 7. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: SHIMHS@yuhs.ac. 8. Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: IJUNG@yuhs.ac. 9. Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: CYLEECS@yuhs.ac. 10. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: CBC1971@yuhs.ac. 11. 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
OBJECTIVES: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. MATERIALS AND METHODS: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. RESULTS: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). CONCLUSIONS: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.
OBJECTIVES: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. MATERIALS AND METHODS: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. RESULTS: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). CONCLUSIONS: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.
Authors: Jennifer L Schehr; Nan Sethakorn; Zachery D Schultz; Camila I Hernandez; Rory M Bade; Diego Eyzaguirre; Anupama Singh; David J Niles; Leslie Henderson; Jay W Warrick; Scott M Berry; Kaitlin E Sundling; David J Beebe; Ticiana A Leal; Joshua M Lang Journal: Biomark Res Date: 2022-04-25