August 17, 2023
´ºÓêÖ±²¥app 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 ´ºÓêÖ±²¥app 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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