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

Am J Clin Pathol. 2020 Feb 8;153(3):387-395. 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.

Keywords: Immune microenvironment; PD-L1; Testicular germ cell tumors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • DNA Mismatch Repair / physiology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism*
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / metabolism*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / surgery
  • Orchiectomy
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Cell Surface / metabolism
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / surgery
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD163 antigen
  • CD274 protein, human
  • CD68 antigen, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Cell Surface

Supplementary concepts

  • Testicular Germ Cell Tumor