Dendritic Cell-based Sequential Chemoimmunotherapy Of Metastatic Colorectal Cancer And The Underlying Immunological Mechanisms

We reported here the immunological mechanisms of dendritic cell based sequential chemoimmunotherapy in treatment of colorectal cancer metastasis. Our studies indicated that appropriate doses of oxaliplatin(OXA) and/or 5-Fu could enhance HLA-A2 and Fas expression, depressed FasL expression on SW480 cell surface and stimulate higher counts of IFN-γsecretion antigen-specific T cells, decrease the productions of immunosuppression cytokines such as IL-10, TGF-β, and VEGF in supernatants of treated SW480 cells, in peripheral blood of patients with metastatic colorectal cancer(MCRC) and CT26 liver metastasis mice models. The proportions of CD4+CD25+ Treg were observed to reduce in PBMCs from MCRC patients or in splenocytes from CT26 liver metastasis mice, as well as CD11b+Gr-1+ MSCs after the chemotherapy. Sequential antigen-pulsed DC administration could stabilize above-mentioned results afterwards. We also found that the production of Hsp70, a new Th1 polarization adjuvant which is a chaperone important to the DCs'cross-presentation, significant increased in peripheral blood of MCRC patients after OXA and 5-Fu chemotherapy. The survival time of CT26 liver metastasis mice had been significant prolonged and specific anti-tumor immune response induced by receiving sequential immuno-chemotherapy. We hope that these results may provide new strategies and methods in clinical trials revolving immunotherapy.