Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma.

Autor:	Gross DJ; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Chintala NK; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Vaghjiani RG; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Grosser R; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Tan KS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Li X; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Choe J; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Li Y; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Union Hospital, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China., Aly RG; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Alexandria University, Alexandria, Egypt., Emoto K; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Keio University School of Medicine, Tokyo, Japan., Zheng H; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China., Dux J; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Cheema W; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Bott MJ; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Travis WD; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Isbell JM; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Li BT; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Jones DR; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Adusumilli PS; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: adusumip@mskcc.org.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2022 Jan; Vol. 17 (1), pp. 89-102. Date of Electronic Publication: 2021 Oct 08.
DOI:	10.1016/j.jtho.2021.09.009
Abstrakt:	Introduction: Patients with stage II to III lung adenocarcinomas are treated with adjuvant chemotherapy (ACT) to target the premetastatic niche that persists after curative-intent resection. We hypothesized that the premetastatic niche is a scion of resected lung tumor microenvironment and that analysis of tumor microenvironment can stratify survival benefit from ACT. Methods: Using tumor and tumoral stroma from 475 treatment-naive patients with stage II to III lung adenocarcinomas, we constructed a tissue microarray and performed multiplex immunofluorescent staining for immune markers (programmed death-ligand 1 [PD-L1], tumor-associated macrophages [TAMs], and myeloid-derived suppressor cells) and derived myeloid-lymphoid ratio. The association between immune markers and survival was evaluated using Cox models adjusted for pathologic stage. Results: Patients with high PD-L1 expression on TAMs or tumor cells in resected tumors had improved survival with ACT (TAMs: hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.12-2.85; tumor cells: HR = 3.02, 95% CI: 1.69-5.40). Among patients with high PD-L1 expression on TAMs alone or TAMs and tumor cells, ACT survival benefit is pronounced with high myeloid-lymphoid ratio (TAMs: HR = 3.87, 95% CI: 1.79-8.37; TAMs and tumor cells: HR = 2.19, 95% CI: 1.02-4.71) or with high stromal myeloid-derived suppressor cell ratio (TAMs: HR = 2.53, 95% CI: 1.29-4.96; TAMs and tumor cells: HR = 3.21, 95% CI: 1.23-8.35). Patients with low or no PD-L1 expression on TAMs or tumor cells had no survival benefit from ACT. Conclusions: Our observation that PD-L1 expression on TAMs or tumor cells is associated with improved survival with ACT provides rationale for prospective investigation and developing chemoimmunotherapy strategies for patients with lung adenocarcinoma. (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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