Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer

Fanyi Gan; Chuanfen Zhang; Liang Xia; Senyi Deng

doi:10.21037/tcr-21-1644

Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer

Transl Cancer Res. 2022 Jan;11(1):3-13. doi: 10.21037/tcr-21-1644.

Authors

Fanyi Gan^#^{1

2}, Chuanfen Zhang^#^{1

2}, Liang Xia^{1

2}, Senyi Deng^{1

2}

Affiliations

¹ Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
² Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Immunotherapy has emerged as a promising treatment strategy in malignant tumors. Inhibitors and neutralizing antibodies targeted PD-1 or PD-L1 show improved clinical outcomes in advanced non-small cell lung cancers (NSCLCs). Previous studies concluded that PD-1 was mainly expressed on activated T cells, B cells and other immune cells. Recently, two studies suggested that PD-1 could be detected in the tumor cells of melanoma and hepatocellular carcinoma. Tumor-endogenous PD-1 in NSCLCs has not been reported at present. Thus, we intended to explore the expression and prognostic relevance of tumor-endogenous PD-1 in NSCLCs.

Methods: We detected the PD-1 expression in fresh tumor samples and tumor slices by flow cytometer and immunohistochemical analysis respectively. Overall survival (OS) and dis-ease-free survival (DFS) were analyzed with Kaplan-Meier survival curve. We explored the PD-1 expression in lung cancer cell lines and investigated its effect on cell proliferation.

Results: Flow cytometry showed that tumor cells with endogenous PD-1 constituted 2.08%, 2.42%, 1.79%, and 1.21% in 4 clinical NSCLC samples respectively. Thirty-four patients (34%) in the cohort were positive for tumor-endogenous PD-1 in IHC analysis. Patients with tumor-endogenous PD-1 had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified tumor-endogenous PD-1 as an independent risk factor (HR =3.807, 95% CI: 2.031-7.135, P<0.05). PD-1 could be observed in 4 kinds of lung cancer cell lines (A549, H1975, H1299 and HCC827). PD-1 overexpression could enhance proliferation and clone formation of these cell lines.

Conclusions: PD-1 was endogenously expressed on the tumor cells of NSCLCs, and it could serve as an independent prognostic risk factor. The molecular mechanism of inferior survival of tumor-endogenous PD-1 may attribute to its role in promoting cell proliferation and clone formation. Our results demonstrated the non-immune role of PD-1 in tumor microenvironment and may provide new thinking for the therapy of NSCLCs.

Keywords: Lung cancer; immunotherapy; survival analysis; tumor-endogenous PD-1.