Seminoma subtypes differ in the organization and functional state of the immune microenvironment.

Autor: Savelyeva AV; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA., Medvedev KE; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Jazyk: angličtina
Zdroj: 3 Biotech [3 Biotech] 2023 Mar; Vol. 13 (3), pp. 110. Date of Electronic Publication: 2023 Mar 02.
DOI: 10.1007/s13205-023-03530-1
Abstrakt: Seminoma is the most common type of testicular germ cell tumors (TGCTs) among 15-44 years old men. Seminoma treatments include orchiectomy, platinum-based chemotherapy and radiotherapy. These radical treatment methods cause up to 40 severe adverse long-term side effects including secondary cancers. Immunotherapy based on immune checkpoint inhibitors, which showed its efficiency for many types of cancer, can be important alternative to the platinum-based therapy for seminoma patients. However, five independent clinical trials evaluating the efficiency of immune checkpoint inhibitors for TGCTs treatment were shut down at the phase II due to lacking clinical efficacy and detailed mechanisms of this phenomena are yet to be discovered. Recently we identified two distinct seminoma subtypes based on transcriptomic data and here we focused on the analysis of seminoma microenvironment and its subtype-specific characteristics. Our analysis revealed that less differentiated subtype 1 of seminoma has immune microenvironment with significantly lower immune score and larger fraction of neutrophils. Both are features of the immune microenvironment at an early developmental stage. On the contrary, subtype 2 seminoma is characterized by the higher immune score and overexpression of 21 genes related to senescence-associated secretory phenotype. Seminoma single cell transcriptomic data showed that 9 out of 21 genes are predominantly expressed in immune cells. Therefore, we hypothesized that senescence of immune microenvironment can be one of the reasons for seminoma immunotherapy failure.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03530-1.
Competing Interests: Conflict of interestThe author declares no conflict of interest. The authors have no relevant financial or non-financial interests to disclose.
(© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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