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

AI Article Synopsis

  • Seminoma is the most common testicular germ cell tumor in young men and is treated using methods like surgery, chemotherapy, and radiotherapy, which can cause severe long-term side effects, including secondary cancers.
  • Immunotherapy, particularly with immune checkpoint inhibitors, presents a potential alternative but has shown limited success in clinical trials for treating seminomas.
  • Recent analysis identified two seminoma subtypes with distinct immune microenvironments, suggesting that the less differentiated subtype may have a weaker immune response, contributing to challenges in immunotherapy effectiveness.

Article Abstract

Unlabelled: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981831PMC
http://dx.doi.org/10.1007/s13205-023-03530-1DOI Listing

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