Journal Article

The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma

Ngalamika, Owen, Mwale, Nicholas K., Mutale, Keagan, Mumba, Chibamba, Mapulanga, Victor, Hamasuku, Anglin, Muhimbe, Zoran, Musumali, Jane, Kawimbe, Musonda

2024

Overview

Penile squamous cell carcinoma (PSCC) occurs more frequently in some developing countries compared to developed countries. Infection with HIV and/or high-risk human papillomavirus (hrHPV) are risk factors for penile cancer development. The tumor microenvironment of PSCC may predict prognosis and may inform on the best targets for immunotherapy. We evaluated the immune microenvironment of penile tumors histologically, and determined whether and/or how HIV and/or hrHPV infections affect this tumor microenvironment. We conducted a prospective analytical cross-sectional study in which penile cancer tumors from 35 patients presenting at the University Teaching Hospital in Lusaka, Zambia were histologically staged and assessed for presence of tumor infiltrating immune cells and expression of immune checkpoints. Immunohistochemistry was used to evaluate immune checkpoints and infiltrating immune cells, while multiplex real-time polymerase chain reaction was used for hrHPV genotyping. The median age of all participants was 55 years. About 24% had advanced histological stage, 83% were HIV + , and 63% had hrHPV detected in their tumors using multiplex real-time polymerase chain reaction. PDL1 expression was significantly higher in HIV - participants than HIV + participants (p = 0.02). Tumors with multiple hrHPV infections had a significantly higher number of cells expressing TIM3 than those with one hrHPV (p = 0.04). High grade tumors had a significantly higher infiltrate of FoxP3 + cells (p = 0.02), CD68 + cells (p = 0.01), CD163 + cells (p = 0.01), LAG3 + cells (p = 0.01), PD1 + cells (p = 0.01) and TIM3 + cells (p = 0.03) when compared with low grade tumours. There was significant moderate to strong positive correlation of cells expressing PD1 and LAG3 (⍴ = 0.69; p = 0.0001), PD1 and TIM3 (⍴ = 0.49; p = 0.017) and TIM3 and LAG3 PDL1 (⍴ = 0.61; p = 0.001). In conclusion, the tumor microenvironment of penile squamous cell carcinoma seems to be affected by both HIV and HPV infections. TIM3 appears to be a potential therapeutic target in PSCC patients with hrHPV infections.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Antigens / B7-H1 Antigen - genetics / B7-H1 Antigen - metabolism / Biology and Life Sciences / Breast cancer / Cancer / Carcinoma, Squamous Cell - immunology / Carcinoma, Squamous Cell - pathology / Carcinoma, Squamous Cell - virology / Care and treatment / CD163 antigen / Comparative analysis / Complications and side effects / Cross-Sectional Studies / Developed countries / Developing countries / Development and progression / Diagnosis / Foxp3 protein / Genital cancers / Genotyping / Head & neck cancer / Health aspects / HIV / HIV (Viruses) / HIV infection / HIV Infections - complications / HIV Infections - immunology / HIV Infections - pathology / HIV Infections - virology / Human immunodeficiency virus / Human papillomavirus / Human Papillomavirus Viruses / Humans / Immune checkpoint / Immune system / Immunohistochemistry / Immunotherapy / Infection / Infections / LDCs / Lymphatic system / Lymphocytes / Lymphocytes, Tumor-Infiltrating - immunology / Male / Medical prognosis / Medicine and Health Sciences / Middle Aged / Multiplexing / Oncology, Experimental / Papillomaviridae / Papillomavirus infections / Papillomavirus Infections - complications / Papillomavirus Infections - immunology / Papillomavirus Infections - pathology / Papillomavirus Infections - virology / Papillomaviruses / Patient outcomes / PD-1 protein / Penile cancer / Penile Neoplasms - immunology / Penile Neoplasms - pathology / Penile Neoplasms - virology / Penis / Polymerase chain reaction / Prognosis / Prospective Studies / Real time / Risk factors / Squamous cell carcinoma / Therapeutic targets / Tumor microenvironment / Tumor Microenvironment - immunology / Tumors