August 17, 2023
Keio University School of Medicine
In cancer, Interleukin-6 (IL-6) is known to be involved in tumor growth and progression, as well as suppressing antitumor immune responses by attracting immunosuppressive cells. However, a research group led by Assistant Professor Setsuko Mise and Professor Akihiko Yoshimura of the Department of Microbiology and Immunology at the Keio University School of Medicine has discovered that when the cytokine suppressor SOCS3 is deleted in T-cells, IL-6, originally a pro-tumorigenic ("bad") cytokine that promotes tumor growth, is conversely transformed into a factor that induces potent tumor-killing capabilities.
IL-6 transmits signals into cells via the IL-6 receptor. SOCS3 normally suppresses this signal to maintain homeostasis. The research group demonstrated that deleting SOCS3 in T-cells alters the nature of IL-6's action. This changes the metabolic state, enhancing the ability of tumor-killing cytotoxic T-cells (killer T-cells) while simultaneously reducing immunosuppressive regulatory T-cells. Consequently, the growth of transplanted tumors was significantly suppressed in mice with T-cells lacking SOCS3 expression. Furthermore, when SOCS3 was artificially suppressed in CAR-T cells used to treat human blood cancers, more potent killer T-cells were generated. This enhanced the therapeutic efficacy against human B-cell leukemia in humanized mice and prolonged their survival.
This research is expected to provide a clue for developing effective therapies by targeting SOCS3, even for cancers that are difficult to treat due to high expression of IL-6.
The results of this research were published in Cell Reports , a journal by the American publisher Cell Press, on August 14, 2023, at 11:00 a.m. (US time).
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