Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients

Shuo Wang; Xiujuan Qu; Zhi Li; Xiaofang Che; Lili Cao; Xianghong Yang; Xuejun Hu; Ling Xu; Kezuo Hou; Yibo Fan; Ti Wen; Yunpeng Liu

doi:10.21037/atm-20-968

Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients

Ann Transl Med. 2021 Mar;9(5):397. doi: 10.21037/atm-20-968.

Authors

Shuo Wang^{1

2

3}, Xiujuan Qu^{1

2

3}, Zhi Li^{1

2

3}, Xiaofang Che^{1

2

3}, Lili Cao^{1

2

3}, Xianghong Yang⁴, Xuejun Hu⁵, Ling Xu^{1

2

3}, Kezuo Hou^{1

2

3}, Yibo Fan^{1

2

3}, Ti Wen^{1

2

3}, Yunpeng Liu^{1

2

3}

Affiliations

¹ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.
² Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China.
³ Liaoning Province Clinical Research Center for Cancer, Shenyang, China.
⁴ Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
⁵ Department of Respiratory Medicine, the First Hospital of China Medical University, Shenyang, China.

Abstract

Background: Although immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies.

Methods: A multi-dimensional analysis based on public databases and 2 independent cohorts including 262 patients with lung cancer was performed. Immunohistochemistry (IHC) and fluorescence-based multiplexed staining were used to detect the immune factors.

Results: PD-L1 was observed to have different expressions and regulatory mechanisms between SCC and ADC. PD-L1 was significantly increased from the messenger RNA (mRNA) to protein levels in the SCC group compared with the ADC group. Also, PD-L1 on tumor cells (TCs) was positively correlated with CD8⁺ tumor lymphocyte infiltrates in ADC, but not in SCC. More importantly, PD-L1 was considered to be an independent predictor of overall survival (OS) for ADC patients. In contrast, in SCC patients, PD-1⁺ tumor-infiltrating lymphocytes (TILs) were considered a poor prognostic predictor.

Conclusions: These findings showed that PD-L1 in ADC and PD-1⁺ TILs in SCC respectively indicates T-cell function, which plays a crucial role in determining prognosis. The distinct functions of the biomarkers between ADC and SCC might provide potential avenues for guiding anti-PD-1/PD-L1 immunotherapy.

Keywords: PD-1; PD-L1; Prognostic values; lung adenocarcinoma; squamous cell carcinoma.