title: Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma.
abstract: Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Chuangzhong
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Zaishang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Urology, Affiliated Oncological Hospital of Xinjiang Medical University , Xinjiang, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Urology, The First People's Hospital of Chenzhou , Hunan, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Jieping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China; Center of Medical Imaging & Image-guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Xingsu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China; Center of Medical Imaging & Image-guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China; Center of Medical Imaging & Image-guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China; Center of Medical Imaging & Image-guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Qiankun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Zike
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Ranyi
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China; Center of Medical Imaging & Image-guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in Southern China, Guangzhou, P.R. China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Fangjian
authors.initials: F
authors.lastname: Zhou
keywords: IFNγ; PD-L1; immunohistochemistry; penile cancer; penile cancer cell line; tumor-infiltrating lymphocytes