Abstract
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.
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Data availability
The datasets analyzed during the current study are available from The Cancer Genome Atlas (https://portal.gdc.cancer.gov/). All generated data are included in this manuscript.
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Acknowledgements
Authors would like to thank Dr. Nick V. Grishin for helpful discussions and suggestions. Authors are also grateful to TCGA data portal for providing access to TGCT datasets.
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This work was supported by the grant from the National Institutes of Health GM127390.
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AVS: conceptualization, validation, formal analysis, investigation, writing—original draft, writing—review & editing. KEM: conceptualization, methodology, software, validation, formal analysis, investigation, data curation, visualization, writing—original draft, writing—review & editing.
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Savelyeva, A.V., Medvedev, K.E. Seminoma subtypes differ in the organization and functional state of the immune microenvironment. 3 Biotech 13, 110 (2023). https://doi.org/10.1007/s13205-023-03530-1
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DOI: https://doi.org/10.1007/s13205-023-03530-1