Chronic Interferon Exposure Linked to Immunosuppression in Cancer
A preclinical study uncovered a novel pathway that links chronic IFN-II exposure to mitochondrial dysfunction and ultimately immunosuppression in cancer, creating foundational insights that may point to future therapies that combat immunotherapy resistance. The post Chronic Interferon Exposure Linked to Immunosuppression in Cancer appeared first on GEN - Genetic Engineering and Biotechnology News…
A recent study from the Salk Institute has uncovered an intriguing link between chronic interferon II (IFN-II) exposure and the development of immunosuppression in cancer. Interferons, which are pro-inflammatory cytokines, play a crucial role in the immune system's response to cancer cells, recruiting immune cells to destroy them. However, prolonged exposure to IFN-II appears to transform its effects from beneficial to detrimental.
Senior author Gerald Shadel, PhD, explained that while interferons initially aid the immune system in fighting cancer, chronic exposure can lead to the suppression of the immune response, allowing tumors to grow instead of shrinking. The study, published in the journal Science, reveals that IFN-II exposure triggers mitochondrial dysfunction, leading to the release of mitochondrial genetic material (mtDNA) into the cell and causing a type I interferon (IFN-I) response.
This newly discovered pathway involves the release of ds-mtRNA, which is perceived by the cell as an invader, prompting the production of IFN-I. This, in turn, boosts the synthesis of prostaglandin E2 (PGE2), an immunosuppressive lipid that inhibits the immune system's ability to attack cancer cells. The researchers found that this PROTAGLANDIN E2-mediated immunosuppressive mechanism is a critical factor in immunotherapy resistance, as it allows tumors to evade the immune system even when anti-PD1 therapies are used.
The team's findings suggest that targeting the prostaglandin E2-mediated pathway could be a promising therapeutic approach to combat immunotherapy resistance. By blocking PGE2 synthesis in melanoma cells, the researchers were able to restore the immune system's ability to recognize and combat the cancer cells, leading to tumor regression in 90% of the mice evaluated.
These findings offer new insights into the complex relationship between interferons, mitochondria, and cancer immunotherapy, potentially paving the way for novel treatments that can overcome resistance to immune-based therapies.
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