{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:46:43Z","timestamp":1791586003990,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Kentucky College of Medicine","award":["AI095032"],"award-info":[{"award-number":["AI095032"]}]},{"name":"University of Kentucky College of Medicine","award":["P30CA177558"],"award-info":[{"award-number":["P30CA177558"]}]},{"name":"Markey Cancer Center","award":["AI095032"],"award-info":[{"award-number":["AI095032"]}]},{"name":"Markey Cancer Center","award":["P30CA177558"],"award-info":[{"award-number":["P30CA177558"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-\u03b3, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-\u03b3 production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable (either treated with mitomycin C or irradiated by X-ray) MC38 CRC cells in combination with rGRA6Nt adjuvant and received a challenge implantation of replication-capable MC38 tumor cells, those mice markedly inhibited the growth of the implanted tumors in association with a two-fold increase in CD8+ T cell density within the tumors. In addition, CD8+ T cells of the immunized mice secreted significantly increased amounts of granzyme B, a key mediator of the cytotoxic activity of CD8+ T cells, and IFN-\u03b3 in response to MC38 CRC cells in vitro when compared to the T cells from unimmunized mice. Notably, the protective effects of the immunization were specific to MC38 CRC cells, as the immunized mice did not exhibit a significantly inhibited growth of EL4 lymphoma tumors. These results indicate that rGRA6Nt is a novel and effective protein adjuvant when used in immunizations with non-replicable cancer cells to potently activate the protective immunity specifically against the cancer cells employed in the immunization.<\/jats:p>","DOI":"10.3390\/cells13020111","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T03:49:04Z","timestamp":1704685744000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective in Immunization with Cancer Cells to Activate the Cancer-Specific Protective Immunity and Inhibit the Cancer Growth in a Murine Model of Colorectal Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Rajesh","family":"Mani","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe G.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanal E.","family":"Balu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4797-4876","authenticated-orcid":false,"given":"Qingding","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Rychahou","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-8436","authenticated-orcid":false,"given":"Tadahide","family":"Izumi","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Mark","family":"Evers","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Passardi, A., Canale, M., Valgiusti, M., and Ulivi, P. (2017). Immune checkpoints as a target for colorectal cancer treatment. Int. J. Mol. 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