T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets.

Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.

Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.

Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma.

Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.

British journal of cancer. 2024 Apr 22 [Epub ahead of print]

Rashidul Islam, Jannis Heyer, Miriam Figura, Xiaoyan Wang, Xichen Nie, Benedict Nathaniel, Sivanjah Indumathy, Katja Hartmann, Christiane Pleuger, Monika Fijak, Sabine Kliesch, Florian Dittmar, Adrian Pilatz, Florian Wagenlehner, Mark Hedger, Bruce Loveland, James H Hotaling, Jingtao Guo, Kate L Loveland, Hans-Christian Schuppe, Daniela Fietz

Dept. of Veterinary Anatomy, Histology and Embryology, Justus Liebig University, Giessen, Germany., State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA., Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia., Hessian Centre of Reproductive Medicine, Justus-Liebig-University, Giessen, Germany., Centre of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany., Dept. of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Germany., Burnet Institute, Melbourne, VIC, Australia., Dept. of Veterinary Anatomy, Histology and Embryology, Justus Liebig University, Giessen, Germany. .