IL-21 or synthetic IL-2 treatment drives T cell IFNγ production or expansion, respectively, during adoptive cell therapy of melanoma
نویسندگان
چکیده
Abstract Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) can generate long-term durable responses in patients with melanoma and even successfully treat that are refractory to anti-PD-1 checkpoint blockade. IL-2 is often used expand TILs, however the administration this cytokine induce systemic toxicities patients. Synthetic mimetics have been developed, including neoleukin-2 (Neo2), which has shown enhanced therapeutic efficacy over IL-2, reduced toxicity. IL-21 also TIL promote T expansion. Here, we tested Neo2 or treating mice bearing B16 tumors received ACT melanoma-specific cells (TRP1 Highand TRP1 Low; TCRs recognizing antigen high low affinity). Both could slow growth tumors, curing several mice. We performed single-cell RNA-sequencing on these analyze therapy-induced changes microenvironment. Neo2-treated had a signature primarily expansion, few other associated transcriptional changes. generated profound IFNγ signature, an increase production many types, cells, macrophages, tumor responding interferon-stimulated gene expression. Interestingly, did not expansion as did, but importantly both levels Tregs within tumor. improved granzyme B. Thus, expands generates higher quality anti-tumor cells. Therefore, promising for improving immunotherapies.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.230.01