Alteration Of CD8~+T Cells And TGF-β In Peripheral Blood Of Melanoma Patients Before And After GVAX Therapy And The Clinical Indication

Background:To observe the alteration of immune microenvironment in the peripheral blood of melanoma patients treated with GM-CSF modified tumor cell vaccine(GVAX)and evaluate the clinical significance.Methods:Fifty-six patients with melanoma treated with GVAX were enrolled in the study.Flow cytometry was used to detect the proportion of CD3+lymphocytes,CD4+T cells,CD8+T cells,Tregs,NKs,DC 1 and DC2 before and after GVAX vaccination treatment.Among all the patients,33 patients were randomly selected to detect the concentration of IL-8,IL-10,IFN-γ,TNF-α and TGF-β in the serum using Luminex xmap and enzyme-linked immunoabsorbentassay(ELISA)before and after GVAX treatment.Then the relationship between the immune cells and cytokines with the clinical survival of patients was analyzed.Results:The proportion of CD8+T cells in the peripheral blood significantly increased after GVAX treatment([37.56±12.76]%vs.[34.71±12.30]%,P=0.006).While the proportion of CD4+T cells significantly decreased after GVAX treatment([53.44±13.36]%vs.[56.27±13.15]%,P=0.017),and the ratio of CD4+/CD8+decreased[1.61%(1.37%)vs.1.75%(0.71%),P=0.009].The proportions of NK,Treg,DC 1 and DC2 were not statistically significant between pre-GVAX and post-GVAX.For patients with advanced melanoma,those with a higher proportion of CD8+T cells before vaccination had better media overall survival compared with those with a lower proportion of CD8+T cells(24.90m vs.6.77m,P=0.012).For 33 patients randomly selected,the concentration of TGF-β decreased after GVAX treatment[(8.99±3.06)vs.(10.66±4.28)ng/mL,P=0.006].Meanwhile those with a lower concentration of TGF-β after vaccination had the longer media overall survival(24.40m vs.6.23m,P=0.010).However,no significant changes of IL-8,IL-10,IFN-γand TNF-α were detected in serum after the vaccination(P≥0.05).Conclusion:GVAX vaccine can enhance the ability of CD8+T cells to induce antitumor immunity and decrease the concentration of TGF-β in serum.A higher proportion of CD8+ T cells before GVAX vaccination and a lower concentration of TGF-β after GVAX maybe the predictors of better prognosis for patients with melanoma who received GVAX treatment.