MHC-restricted adaptive immune responses to CT26 colon cancer cell line in allogeneic mixed chimera

다국어 초록 (Multilingual Abstract)

Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance in context of anti-cancer effect is yet unknown. In this study, we investigated the anti-cancer immune response to CT26, a murine colon cancer cell line, when in mixed allogeneic chimeras by performing double bone marrow transplantation (BMT). More specifically, we analyzed donor- and recipient-restricted anti-cancer T cell responses, and phenotypes of subpopulations of T cells. After 50 days post-BMT, 1 X 105 cells of CT26 cells were challenged intrahepatically, we detected the generation of cancer-specific CD4 and CD8 T cells by flow cytometric analysis using CT26 lysates and H-2Ld-restricted-AH1 pentamer at various time points. We found that anti-cancer immunocompetency depends heavily on the cancer-specific CD8 T cell responses in MHC-restricted manner which was also supported by the increase of IFN-γ secreting CD4 T cells. Moreover, we demonstrate that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62LhiCCR7+) as well as effect memory cells (CD62LloCCR7-). 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. Our results suggest that the responses of primary immunocompetency and pre-existing memory T cell against allogeneic cancer are sustained and preserved in mixed allogeneic chimeric environment.

목차 (Table of Contents)

• ABSTRACT 1
• I. Introduction 2 - 3
• II. Materials and Methods 4 - 6
• III. Results 7 - 10
• IV. Disscussion 11 – 12
• V. References 13 - 14