J Cancer 2021; 12(20):6118-6125. doi:10.7150/jca.60739 This issue

Research Paper

Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma

Yuting Zhang1#, Xianyong Chen2#, Hongmei Zheng1, Yuting Zhan1, Jiadi Luo1, Yang Yang1, Yue Ning1, Haihua Wang1, Weiyuan Wang3✉, Songqing Fan1✉

1. Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
2. Department of Pathology, Affiliated Hospital of Xiangnan University, Chenzhou City, Hunan, 423000, China.
3. Department of Pathology, Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Zhang Y, Chen X, Zheng H, Zhan Y, Luo J, Yang Y, Ning Y, Wang H, Wang W, Fan S. Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma. J Cancer 2021; 12(20):6118-6125. doi:10.7150/jca.60739. Available from https://www.jcancer.org/v12p6118.htm

File import instruction

Abstract

Graphic abstract

Aims: Programmed cell death ligand 1 (PD-L1) is the ligand of programmed death 1 (PD-1), which is a host immunity inhibitory receptor. Expression of PD-L1 in diverse tumor types has been widely discussed, while there is little research about tumor intrinsic-PD-1. Phospho-S6 (p-S6) is an important downstream effector in the PI3K/AKT/mTOR pathway. Our study was focused on investigating expression of cancer cell-intrinsic PD-1, PD-L1 and p-S6 proteins and aimed to illustrate their relationship and clinical significances in nasopharyngeal carcinoma (NPC).

Methods: The expression of PD-1, PD-L1 and p-S6 proteins in tissues of NPC, non-cancerous nasopharyngeal epithelia, primary cancer and matching metastatic lesion was detected by immunohistochemistry.

Results: Expression of PD-1, PD-L1 and p-S6 proteins and co-expression of PD-1 and PD-L1 were significantly higher in NPC (all P<0.05). The expression of PD-1 and co-expression of PD-1 and PD-L1 in paired metastatic NPC were significantly increased (all P<0.01). NPC patients with positive expression of PD-L1 showed significantly higher overall survival rate (P =0.035). However, NPC patients with positive expression PD-1 and p-S6 showed significantly lower overall survival rate (P =0.031, P=0.044, respectively). Interestingly, NPC patients with co-expression of PD-1 and PD-L1 had lower overall survival rate (P=0.042). Multivariate Cox proportional hazard regression analysis confirmed that positive expression of PD-L1 and p-S6 were independent prognostic factors for NPC patients.

Conclusions: Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 proteins, PD-L1 might serve as a good prognostic biomarker, while p-S6 could be an independent poor prognostic biomarker for NPC patients.

Keywords: nasopharyngeal carcinoma, cancer cell-intrinsic PD-1, PD-L1, p-S6, prognosis