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• W4361951036 abstract "<div>Abstract<p><b>Purpose:</b> Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8⁺ T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8⁺ T cells recently found to constitute the majority of tumor-specific T cells.</p><p><b>Experimental Design:</b> We used an agonistic anti–4-1BB antibody added during the initial tumor fragment cultures to provide <i>in situ</i> 4-1BB costimulation.</p><p><b>Results:</b> We found that addition of an agonistic anti–4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8⁺ TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8⁺ T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8⁺ T cells with anti–4-1BB, suggesting that an ongoing HLA class I–mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8⁺ TIL outgrowth.</p><p><b>Conclusions:</b> Our results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. <i>Clin Cancer Res; 21(3); 611–21. ©2014 AACR.</i></p></div>" @default.
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• W4361951036 date "2023-03-31" @default.
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• W4361951036 title "Data from Manipulating the Tumor Microenvironment <i>Ex Vivo</i> for Enhanced Expansion of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy" @default.
• W4361951036 doi "https://doi.org/10.1158/1078-0432.c.6522762.v1" @default.
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