Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma.
J Thorac Oncol
; 17(1): 89-102, 2022 01.
Article
en En
| MEDLINE
| ID: mdl-34634452
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adenocarcinoma del Pulmón
/
Neoplasias Pulmonares
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Thorac Oncol
Año:
2022
Tipo del documento:
Article