biostudies-literatureNowicki TSTodd and Donna JonesParker Institute for Cancer ImmunotherapyKen and Donna SchultzHyundai Hope On WheelsRessler Family FundRuby Family FoundationNational Cancer InstituteNCI NIH HHSCalifornia Institute for Regenerative MedicineThomas Stutz1589-1597https://www.ebi.ac.uk/biostudies/studies/S-EPMC10702871biostudies-literatureUnknown11(12)Transgenic T-cell receptor (TCR) T cell-based adoptive cell therapies for solid tumors are associated with dramatic initial response rates, but there remain many instances of treatment failure and disease relapse. The association of infusion product cytokine profiles with clinical response has not been explored in the context of TCR T-cell therapy products. Single-cell antigen-dependent secretomic and proteomic analysis of preinfusion clinical TCR T-cell therapy products revealed that TNFα cytokine functionality of CD8+ T cells and phospho-STAT3 signaling in these cells were both associated with superior clinical responsiveness to therapy. By contrast, CD4+ T-helper 2 cell cytokine profiles were associated with inferior clinical responses. In parallel, preinfusion levels of IL15, Flt3-L, aCancer immunology researchInfusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy.PMC10702871CLIN2-11380P30 CA016042R35 CA197633K08 CA241088Hope Scholar AwardK08 CA 241088P01 CA244118Ribas AKawakami MKidd CKQuiros CPeters CWKlomhaus AMBaselga-Carretero IKaplan-Lefko PPerez Garcilazo IBerent-Maoz BComin-Anduix BNowicki TSMacabali MHfalseInfusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy.Transgenic T-cell receptor (TCR) T cell-based adoptive cell therapies for solid tumors are associated with dramatic initial response rates, but there remain many instances of treatment failure and disease relapse. The association of infusion product cytokine profiles with clinical response has not been explored in the context of TCR T-cell therapy products. Single-cell antigen-dependent secretomic and proteomic analysis of preinfusion clinical TCR T-cell therapy products revealed that TNFα cytokine functionality of CD8+ T cells and phospho-STAT3 signaling in these cells were both associated with superior clinical responsiveness to therapy. By contrast, CD4+ T-helper 2 cell cytokine profiles were associated with inferior clinical responses. In parallel, preinfusion levels of IL15, Flt3-L, a2023-01-01T00:00:00Z2023 Dec2025-04-03T23:55:20.57Z2024-11-14T08:53:08.669ZS-EPMC107028713787133310.1158/2326-6066.CIR-23-0577