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- W4313368541 abstract "Abstract Accessibility of T cell transfer therapies is hindered by cost and time required for product development. We found that shortening ex vivo expansion of Th17 cells licenses a proinflammatory cell product which induces cytokine storm with high levels of systemic IL-6 in tumor-bearing hosts. Unique from other helper subsets, briefly expanded Th17 cells eradicate large tumors in low doses and generate long-lived memory against tumor rechallenge, suggesting a benefit to the inflammatory state. As the toxicity of cytokine release is managed in patients through IL-6 blockade, we addressed the physiologic impact of IL-6 on efficacy and durability of Th17 cell therapy in this immunocompetent model. We hypothesized that peak IL-6 induced by Th17 cells was critical to their durable memory properties. To address this, we used the TRP-1 transgenic mouse model where CD4+ T cells express a TCR that recognizes TRP-1 of B16F10 melanoma. Acute IL-6 blockade post Th17 transfer did not impact the primary antitumor response, yet abrogated long-term responses by promoting tumor relapse upon secondary challenge. Mechanistically, IL-6 blockade reduced pSTAT3 and Bcl2 in transferred T cells and promoted a greater frequency of FoxP3+ Treg cells in the peripheral blood and tumor-draining lymph nodes. Finally, serum IL-6 was inversely correlated with engraftment of tumor-specific Tregs from the transferred product. Overall, short-term expanded Th17 cells uniquely induce IL-6, which promotes Th17 survival, suppresses engraftment of tumor-specific Tregs, and is critical to durable memory. This work may suggest that the universal strategy to inhibit IL-6 during cytokine release syndrome may come at the expense of long-term efficacy for cell therapy." @default.
- W4313368541 created "2023-01-06" @default.
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- W4313368541 date "2020-05-01" @default.
- W4313368541 modified "2023-09-26" @default.
- W4313368541 title "IL-6 fuels durable memory for Th17 cell-mediated responses to tumors" @default.
- W4313368541 doi "https://doi.org/10.4049/jimmunol.204.supp.246.4" @default.
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