The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Abstract

Penile cancer is an extremely rare malignancy that accounts for approximately 1% of cancer deaths in the United States every year. While primary penile cancer can be managed surgically, advanced and metastatic forms of the disease require more aggressive management plans with systemic chemotherapy and/or radiotherapy. Despite the meaningful response to systemic treatments, the 2-year progression-free survival and disease-specific survival have shown disappointing results. Therefore, there is a crucial need for alternative treatment options with more favorable outcomes and a lower toxicity profile. There are currently extensive studies of tumor molecular biology and clinical trials with targeted molecular therapies, such as PD-1, PD-L1, and CTLA-4. In this review, we will describe the penile cancer microenvironment, and summarize the rationale for immunotherapy in penile cancer patients.

Whole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell Carcinoma

“…Research. Our study provides several novel insights into PSCC biology and highlights the similarities with HNSC, taking advantage of WES analysis, in a rare cancer with limited therapeutic choices 7,8,10,44 . The goal was to exploit this technology to gain potential insights into new therapeutic strategies in this rare and lethal cancer.…”

National trends and survival outcomes of penile squamous cell carcinoma based on human papillomavirus status

“… 34 Other markers, such as programmed death ligand 1 (PD‐L1), have been found mostly in HPV‐negative tumors. 8 , 35 Unlike HPV + tumors, these lack p16INK4A as a surrogate immunohistochemistry marker. 9 , 11 , 36 When considering all the available evidence, it is apparent HPV‐dependent and independent tumors arise from different molecular pathways, but genetic alterations from both lead to the disruption of related tumor‐suppressing pathways.…”

“…Although there have been advances in the understanding of penile carcinogenesis and tumor microenvironment, 8 , 9 the unique molecular mechanisms underlying pSCC remain poorly understood. At present, tumors are thought to arise from progression of precursor lesions arising from separate HPV‐dependent and HPV‐independent pathways.…”

Tislelizumab Combination With Chemotherapy Successfully Converted Unresectable Advanced Penile Cancer Into Complete Surgical Excision: a Case Report and Literature Review

“…Patients with HPV + PSCC have a better prognosis than those with HPV − . The possible mechanism is that the virus increases the production of neo-antigens, while increasing the number of in ltrating CD8 + T cells in the tumor microenvironment [10]. Does this mean that the HPV virus could be a meaningful biomarker for immunotherapy?…”