Tumor and tumor-associated macrophage programmed death-ligand 1 expression is associated with adjuvant chemotherapy benefit in lung adenocarcinoma Journal Article
| Authors: | Gross, D. J.; Chintala, N. K.; Vaghjiani, R. G.; Grosser, R.; Tan, K. S.; Li, X.; Choe, J.; Li, Y.; Aly, R. G.; Emoto, K.; Zheng, H.; Dux, J.; Cheema, W.; Bott, M. J.; Travis, W. D.; Isbell, J. M.; Li, B. T.; Jones, D. R.; Adusumilli, P. S. |
| Article Title: | 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. © 2021 International Association for the Study of Lung Cancer |
| Keywords: | nsclc; premetastatic niche; tumor immune microenvironment; mdscs; myeloid-lymphoid ratio |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 17 |
| Issue: | 1 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-01-01 |
| Start Page: | 89 |
| End Page: | 102 |
| Language: | English |
| DOI: | 10.1016/j.jtho.2021.09.009 |
| PUBMED: | 34634452 |
| PROVIDER: | scopus |
| PMCID: | PMC8692446 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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