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• W4362545758 abstract "<div>Abstract<p>Immunogenic tumors grow progressively even when heavily infiltrated by CD8⁺ T cells. We investigated how to rescue CD8⁺ T-cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1⁺ tumor-specific CD8⁺ T cells that were dysfunctional. Treatment with αPD-L1– and αCTLA-4–blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using <i>Salmonella</i> Typhimurium A1-R (A1-R) to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8⁺ T-cell response: Proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8⁺ T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1-blocking antibody enhanced the expansion of tumor-specific CD8⁺ T cells and resulted in 80% tumor rejection. Collectively, these data show a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8⁺ T cells and eradicate advanced immunogenic tumors. <i>Cancer Immunol Res; 1(2); 123–33. ©2013 AACR</i>.</p></div>" @default.
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• W4362545758 date "2023-04-03" @default.
• W4362545758 modified "2023-10-16" @default.
• W4362545758 title "Data from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer" @default.
• W4362545758 doi "https://doi.org/10.1158/2326-6066.c.6548200.v1" @default.
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