| 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. |
