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• W4386208439 abstract "Abstract To investigate the effect of a major histocompatibility complex class I (MHC-I) overexpression to augment immune sensitivity against tumors, we have generated the murine colorectal carcinoma cell line MC38 (with the endogenous H-2 b haplotype) overexpressing the allogeneic mouse MHC-I cell surface molecule H-2K d (MC38 H-2K d ). The tumorigenicity of unmodified parental cells (MC38 PT) and MC38 H-2K d was tested in vivo by subcutaneous injection into the flank of wild-type (WT) and programmed death-1 (PD-1) knockout (KO) mice in a C57BL/6 (H-2 b ) genetic background. MC38 PT cells readily formed tumors and grew progressively in both WT and PD-1 KO mice. The speed of MC38 PT tumor growth was slower in PD-1 KO mice than in WT mice. In contrast, MC38 H-2K d cells showed full sensitivity to rejection by the immune system in both naïve WT and PD-1 KO mice, indicated by spontaneous tumor regression. Next, we sought to determine the extent to which H-2K d -overexpressing tumors could protect the mice against unmodified cancers. PD-1 KO mice were first sensitized with highly immunogenic MC38 H-2K d cells and then challenged with weakly immunogenic MC38 PT cells. Intriguingly, all PD-1 KO mice gained immunity against the aggressive MC38 tumor and became tumor-free. Sensitizing PD-1 KO mice with growth-arrested (by the pre-treatment with mitomycin C, MMC) and the debris of MC38 H-2K d tumors also provided full protection against the growth of secondary MC38 PT tumors. Most notably, sensitization with the debris of MC38 H-2K d cells provided the long-term immunological memory against MC38 PT carcinoma cells. This finding implies that MC38 H-2K d cells retain highly efficient and durable immunogenicity." @default.
• W4386208439 created "2023-08-29" @default.
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• W4386208439 date "2023-08-28" @default.
• W4386208439 modified "2023-10-01" @default.
• W4386208439 title "Sensitization with an allogeneic MHC class I molecule induces anti-tumor immunity in the absence of PD-1 in mice" @default.
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• W4386208439 doi "https://doi.org/10.1101/2023.08.26.554968" @default.
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