Major Histocompatibilty Complex–Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera

• Published in: Transplantation proceedings 2017-06, Vol.49 (5), p.1153-1159
• Main Authors: Lee, K.W, Choi, B, Kim, Y.M, Cho, C.W, Park, H, Moon, J.I, Choi, G.-S, Park, J.B, Kim, S.J
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Transplantation; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Chimera - immunology; Colonic Neoplasms - immunology; Immunity, Humoral; Major Histocompatibility Complex - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Surgery; Transplantation, Homologous
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2017.03.011

Abstract Background Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. Methods We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 105 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2Ld -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4+ and CD8+ T cells at various time points. Results We found that immunocompetence against tumors depends heavily on cancer-specific CD8+ T-cell responses in a major histocompatibility complex–restricted manner; the evidence was further supported by the increase of interferon-γ–secreting CD4+ T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62Lhi CCR7+ ) as well as effector memory cells (CD62Llo CCR7− ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Conclusions Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment.