Project Details
Projekt
Role of regulatory T cells and type 17 T cells in testicular germ cell cancer and testicular inflammation
Subject Area
Reproductive Medicine, Urology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 515636567
Testicular cancer is one of the most common malignancies in young men aged 15-44 years with a steadily growing incidence worldwide. The vast majority among biologically diverse subsets of testicular cancers are testicular germ cell tumors (TGCT) which arise from pre-invasive germ cell neoplasia in situ (GCNIS). Although a large proportion of TGCTs is confined to the testis and can be cured by surgery, about 20-30% still require systemic chemotherapy and can metastasize and/or relapse. The infiltration of immune cells has been identified as a hallmark for TGCT, but the impact on tumour development, progression, and prognosis are still poorly understood. Despite histopathological similarities in early stages of testicular neoplasia, the composition of leukocyte infiltrates differs strikingly from non-malignant disease, i.e. low-grade testis inflammation in infertile men. In contrast to the physiological milieu (immune privilege), mainly T lymphocytes accumulate under pathological conditions, and represent the majority of the tumor infiltrating lymphocytes (TIL) along with increased numbers of macrophages, dendritic cells, and B cells in TGCT. T cells can be further divided into CD4+ T helper (Th) and CD8+ T cytotoxic cells (Tc). Th and Tc can be stratified into a plethora of subpopulations. Of special interest in cancer research are regulatory T cells (Treg) and IL-17 producing Th and Tc cells. Those have been linked to tumor progression and prognosis in other cancer entities, while respective data are lacking for TGCT. Project 6 “Role of regulatory T cells and type 17 T cells in testicular germ cell cancer and testicular inflammation” as part of the FOR ‘INFINITE’ aims to i) analyze Treg and type 17 T cell presence in TGCT and testicular inflammation associated with clinical parameters, ii) characterize the direct and indirect effects of Treg and type 17 T cells on tumor cells (and vise versa) in vitro, and iii) establish an ex vivo culture model and decipher transcriptional profiles of T cells and tumor cells in TGCT. By combining experimental approaches such as flow cytometry, transcriptomics (bulk and single cell RNA sequencing), spatial transcriptomics as well as sophisticated imaging (i.e. CODEX) and cellular interaction analysis (i.e. NicheNet), we will be able to unveil the impact of Treg and type 17 T cells in testicular inflammation and TGCT to better understand the tumor microenvironment which can be used for further interventional studies to ultimately aim at personalized immunomodulatory therapy of testicular cancer.
DFG Programme
Research Units
Subproject of
FOR 5644:
The role of immune cells in the function of the normal and diseased testis and epididymis (‘INFINITE’)
International Connection
Australia, China
Cooperation Partners
Professor Jingtao Guo, Ph.D.; Professorin Kate Loveland, Ph.D.
