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Decoding the Role of Interleukin-30 in the Crosstalk Between Cancer and Myeloid Cells
1Department of Medicine and Sciences of Aging, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Abstract:
In the last few years, a new actor hit the scene of the tumor microenvironment, the p28 subunit of interleukin (IL)-27, known as IL-30. Its molecular structure allows it to function as an autonomous cytokine and, alternatively, to pair with other subunits to form heterodimeric complexes and enables it to play different, and not fully elucidated, roles in immunity. However, data from the experimental models and clinical samples, suggest IL-30's engagement in the relationship between cancer and myeloid cells, which fosters the tumor microenvironment and the cancer stem cell niche, boosting the disease progression. Activated myeloid cells are the primary cellular source and one of the targets of IL-30, which can also be produced by cancer cells, especially, in aggressive tumors, as observed in the breast and prostate. This review briefly reports on the immunobiology of IL-30 and related cytokines, by comparing mouse and human counterparts, and then focuses on the mechanisms whereby IL-30 amplifies intratumoral myeloid cell infiltrate and triggers a vicious cycle that worsens immunosuppression in the tumor microenvironment (TME) and constitutes a real threat for a successful immunotherapeutic strategy.
Insights
Interleukin-30 (IL-30), a subunit of IL-27, promotes tumor progression by enhancing myeloid cell activity within the tumor microenvironment. This creates immunosuppression, hindering effective cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The p28 subunit of interleukin (IL)-27, known as IL-30, has emerged as a key player in the tumor microenvironment.
- IL-30 exhibits diverse functions, acting autonomously or forming heterodimeric complexes, with roles in immunity that are not fully understood.
Purpose of the Study:
- To review the immunobiology of IL-30 and related cytokines, comparing human and mouse models.
- To elucidate the mechanisms by which IL-30 promotes tumor progression and immunosuppression.
Main Methods:
- Literature review focusing on experimental models and clinical samples.
- Comparative analysis of IL-30's role in mouse and human systems.
- Examination of IL-30's impact on myeloid cell infiltration and function.
Main Results:
- IL-30 is implicated in the interplay between cancer and myeloid cells, fostering the tumor microenvironment and cancer stem cell niche.
- Activated myeloid cells are a primary source and target of IL-30, which can also be produced by aggressive cancer cells.
- IL-30 amplifies intratumoral myeloid cell infiltration, creating a cycle of immunosuppression within the tumor microenvironment (TME).
Conclusions:
- IL-30 significantly contributes to tumor progression and immune evasion.
- The immunosuppressive effects of IL-30 pose a substantial challenge to successful cancer immunotherapy strategies.
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