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Four-color Fluorescence Immunohistochemistry of T-cell Subpopulations in Archival Formalin-fixed, Paraffin-embedded Human Oropharyngeal Squamous Cell Carcinoma Samples

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

Chibamba Mumba¹, Zoran Muhimbe¹, Victor Mapulanga²

¹Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia.

|May 1, 2024

Summary

Penile squamous cell carcinoma (PSCC) tumor microenvironment is impacted by HIV and high-risk human papillomavirus (hrHPV) infections. TIM3 shows potential as a therapeutic target for PSCC patients with hrHPV.

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Published on: March 8, 2012

Area of Science:

Oncology
Immunology
Virology

Background:

Penile squamous cell carcinoma (PSCC) incidence varies globally, with HIV and high-risk human papillomavirus (hrHPV) as key risk factors.
The tumor microenvironment (TME) in PSCC is crucial for prognosis and potential immunotherapy targets.
Understanding the interplay between infections and TME is vital for advancing PSCC treatment.

Purpose of the Study:

To evaluate the immune microenvironment of penile tumors.
To determine the impact of HIV and/or hrHPV infections on the PSCC tumor microenvironment.
To identify potential immunotherapy targets within the PSCC TME.

Main Methods:

Prospective analytical cross-sectional study of 35 PSCC patients in Lusaka, Zambia.
Histological staging and assessment of tumor-infiltrating immune cells and immune checkpoints.
Immunohistochemistry for immune cell and checkpoint evaluation; multiplex real-time PCR for hrHPV genotyping.

Main Results:

83% of patients were HIV-positive, and 63% had detectable hrHPV.
PDL1 expression was higher in HIV-negative patients (p=0.02).
TIM3 expression was higher in tumors with multiple hrHPV infections (p=0.04). High-grade tumors showed increased infiltration of FoxP3+, CD68+, CD163+, LAG3+, PD1+, and TIM3+ cells. Significant correlations were observed between PD1, LAG3, and TIM3 expression.

Conclusions:

HIV and hrHPV infections significantly affect the penile cancer tumor microenvironment.
TIM3 is a potential therapeutic target for PSCC patients with hrHPV infections.
Immune checkpoint expression correlates with tumor grade and specific infections, highlighting TME complexity.