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

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.

• Authors: Daniel J Gross, Navin K Chintala, Raj G Vaghjiani, Rachel Grosser, Kay See Tan, Xiaoyu Li, Jennie Choe, Yan Li, Rania G Aly, Katsura Emoto, Hua Zheng, Joseph Dux, Waseem Cheema, Matthew J Bott, William D Travis, James M Isbell, Bob T Li, David R Jones, Prasad S Adusumilli
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 17 Issue 1 Pg. 89-102 (01 2022) ISSN: 1556-1380 [Electronic] United States
• PMID: 34634452 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor

Topics

• Adenocarcinoma of Lung (drug therapy)
• B7-H1 Antigen (therapeutic use)
• Biomarkers, Tumor
• Chemotherapy, Adjuvant
• Humans
• Lung Neoplasms (drug therapy)
• Prognosis
• Prospective Studies
• Tumor Microenvironment
• Tumor-Associated Macrophages