Multiplex Immunofluorescence Captures Progressive Immune Exhaustion with Advancing Penile Squamous Cell Cancer Stage.

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

Cancers. 2024 Jan 11*** epublish ***

Filip Ionescu, Jonathan Nguyen, Carlos Moran Segura, Mahati Paravathaneni, G Daniel Grass, Peter Johnstone, Niki M Zacharias, Curtis A Pettaway, Xin Lu, Youngchul Kim, Junmin Whiting, Jasreman Dhillon, Steven A Eschrich, Juskaran Chadha, Keerthi Gullapalli, Gabriel Roman Souza, Hiroko Miyagi, Brandon J Manley, Philippe E Spiess, Jad Chahoud

Genitourinary Oncology Department, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Pathology Department, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Radiation Oncology Department, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Biological Sciences, University of Notre Dame, Norte Dame, IN 46556, USA., Biostatistics and Bioinformatics Department, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.