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More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy. vaccines TSAmodified modified vivo TSAtreated treated Nutu19 Nutu 19 Nutu-1 Xray X ray staining GMCSF, GMCSF GM CSF, CSF GM-CSF IL7, IL7 IL 7, 7 IL-7 IL17, IL17 17, 17 IL-17 LIF LIX KC MCP1, MCP1 MCP 1, 1 MCP-1 MIP2, MIP2 MIP 2, 2 MIP-2 MCSF, MCSF M M-CSF IP10/CXCL10, IP10CXCL10 IPCXCL IP 10/CXCL10, 10 CXCL10 CXCL IP-10/CXCL10 MIGCXCL9 MIGCXCL MIG CXCL9 MIG/CXCL9 RANTES IL4, IL4 4, 4 IFNγ, IFNγ IFN γ, γ immunoassay cellmediated mediated tumorbearing bearing CD4 CD CD8 P<0.05. P005 P P<0.05 . 0 05 (P<0.05) extent IL- effect exposure progression system rates Nutu1 Nutu- IL1 IL-1 MCP- MIP- IP10 IP10/CXCL10 IP10CXCL1 10CXCL10 10/CXCL10 CXCL1 IP-10/CXCL1 MIG/CXCL P00 P<0.0 (P<0.05 IP1 IP10/CXCL1 IP10CXCL 10CXCL1 10/CXCL1 IP-10/CXCL P0 P<0. (P<0.0 IP10/CXCL 10CXCL 10/CXCL P<0 (P<0. P< (P<0 (P< (P