Mani Rajesh, Evers B Mark, Suzuki Yasuhiro
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Department of Surgery, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Med Res Arch. 2025 Jun;13(6). doi: 10.18103/mra.v13i6.6615. Epub 2025 Jun 30.
Our recent study demonstrated that immunizations with nonreplicable MC38 colorectal cancer cells plus a novel recombinant protein adjuvant, the amino-terminus region of dense granule protein 6 (rGRA6Nt) of (a protozoan parasite), effectively activate the cancer cell-specific CD8 T cytotoxic cells and inhibit the growth of implanted tumors of the identical cancer cells after its challenge implantation. In the present study, we first examined whether rGRA6Nt activates mRNA expression for IFN-γ, IL-12, IL-15, and IL-18, which are known to assist an activation of the CD8 T cells, in innate immune cells. Following an intraperitoneal injection of rGRA6Nt (40 μg) into SCID mice deficient in both T and B cells, markedly increased levels of mRNA for only IFN-γ and IL-18 were detected in their peritoneal exudate innate immune cells. When C57BL/6 mice were immunized with nonreplicable MC38 colorectal cancer cells plus rGRA6Nt adjuvant twice and challenged with replication-capable cancer cells of the identical colorectal cancer, more than one fifth (22.2%, 6/27) of the immunized mice rejected the growth of the implanted tumors, whereas none (0/27, <0.05) of unimmunized control mice rejected the implanted tumors. These results indicate that rGRA6Nt protein adjuvant has a unique capability to selectively activate expression of IFN-γ and IL-18 in innate immune cells, and that immunizations with nonreplicable cancer cells in combination with this protein adjuvant can induce a protection to reject the growth of the identical tumor cells after its challenge implantation in a significant portion of the immunized mice.
我们最近的研究表明，用不可复制的MC38结肠癌细胞加上一种新型重组蛋白佐剂——疟原虫致密颗粒蛋白6（rGRA6Nt）的氨基末端区域进行免疫，能有效激活癌细胞特异性CD8 T细胞毒性细胞，并在植入相同癌细胞后抑制其植入肿瘤的生长。在本研究中，我们首先检测了rGRA6Nt是否能激活先天性免疫细胞中已知有助于CD8 T细胞激活的IFN-γ、IL-12、IL-15和IL-18的mRNA表达。在向T和B细胞均缺陷的SCID小鼠腹腔注射rGRA6Nt（40μg）后，在其腹腔渗出液先天性免疫细胞中仅检测到IFN-γ和IL-18的mRNA水平显著升高。当用不可复制的MC38结肠癌细胞加rGRA6Nt佐剂对C57BL/6小鼠进行两次免疫，然后用相同结肠直肠癌的可复制癌细胞进行攻击时，超过五分之一（22.2%，6/27）的免疫小鼠排斥植入肿瘤的生长，而未免疫的对照小鼠无一（0/27，<0.05）排斥植入肿瘤。这些结果表明，rGRA6Nt蛋白佐剂具有独特的能力，能选择性激活先天性免疫细胞中IFN-γ和IL-18的表达，并且用不可复制的癌细胞与这种蛋白佐剂联合免疫可诱导保护作用，使相当一部分免疫小鼠在植入攻击后排斥相同肿瘤细胞的生长。
