Differences in PD-L1–Expressing Macrophages and Immune Microenvironment in Testicular Germ Cell Tumors

• Published in: American journal of clinical pathology Vol. 153; no. 3; pp. 387 - 395
• Main Authors: Sadigh, Sam, Farahani, Sahar J, Shah, Abhishek, Vaughn, David, Lal, Priti
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08.02.2020
• Subjects: Adolescent; Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; B7-H1 Antigen - metabolism; Biomarkers, Tumor - metabolism; CD163 antigen; Cellular signal transduction; Choriocarcinoma; Development and progression; DNA Mismatch Repair - physiology; Forkhead Transcription Factors - metabolism; Foxp3 protein; Germ cell tumors; Health aspects; Humans; Immunohistochemistry; Immunological research; Lymphocytes; Macrophages; Macrophages - metabolism; Membrane proteins; Metastases; Metastasis; Middle Aged; Mismatch repair; Neoplasms, Germ Cell and Embryonal - metabolism; Neoplasms, Germ Cell and Embryonal - pathology; Neoplasms, Germ Cell and Embryonal - surgery; Orchiectomy; PD-1 protein; PD-L1 protein; Physiological aspects; Prognosis; Programmed Cell Death 1 Receptor - metabolism; Receptors, Cell Surface - metabolism; Seminoma; Testes; Testicular cancer; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Testicular Neoplasms - surgery; Tumor cells; Tumor Microenvironment - immunology; Tumor-infiltrating lymphocytes; Tumors; Young Adult; United States; Testicular germ cell tumors; Immune microenvironment; PD-L1
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqz184

Abstract Objectives To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers. Methods Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated. PDL-1 expression was evaluated on tumor cells and macrophages. Results GCTs primarily express PD-L1 on TAMs, except choriocarcinoma, where true tumor cell positivity was noted. Seminomas reveal increased intratumoral PD-L1+ TAMs compared with NSGCTs (P < .05). Activated TILs are increased in NM-seminomas compared with M-seminomas (P < .05). All GCTs retained MMR expression. Conclusions Robust PD-L1+ TAMs are significantly expanded in seminomas compared with NSGCTs. Among all GCTs, only choriocarcinoma cells reveal true positivity for PD-L1. These findings expand the realm of potentially targeted treatments for GCTs.