Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

Abstract

Purpose: Autologous melanoma cells display a broad variety of tumor antigens and were used for treatment of American Joint Committee on Cancer stages III and IV melanoma as an adjuvant or active therapy. Survival data and immune response were evaluated in vaccinated patients. Experimental Design: Forty-seven patients received 2,4-dinitrophenyl–conjugated autologous melanoma vaccine as an adjuvant (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood sampled before vaccination and after five or eight vaccine doses was evaluated against melanoma cells and autologous peripheral blood mononuclear cells using IFNγ enzyme–linked immunospot. Serum levels of antilivin, an inhibitor of apoptosis, and anti-gp100 IgG were determined. Results: The immunologic effect of the vaccine differed between the two groups of patients. In the adjuvant group, there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035) after vaccination and an increase in antimelanoma CD4 T cells correlating with improved overall survival (P = 0.04). In the therapeutic group, there was no objective tumor regression; antimelanoma T-cell reactivity increased by a small amount, stayed the same, or in some cases decreased. In all patients, a significant increase was noted in CD4 T-cell reactivity against autologous peripheral blood mononuclear cells (P = 0.02), which did not affect survival. Increased antilivin IgG was associated with improved survival. Expression of MHC class II on melanoma cells was vital for the immunogenicity of the vaccine. Conclusion: Autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival. Patients with active metastatic disease generally displayed reduced immune response and gained little from active immunization.

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

“…It is also clear that alterations in the expression of CIITA, MHCI, and/or MHCII molecules can influence the immune response against tumors. In both murine models and human studies, the expression of CIITA, MHCI, and/or MHCII molecules can influence antitumor immune responses (41)(42)(43). Consistent with this, the expression of MHCI and/or MHCII molecules on tumor cells has been repeatedly shown to impact prognosis (44)(45)(46).…”

MHC class II expression in pancreatic tumors: a link to intratumoral inflammation

“…Consequently, in various clinical trials, e.g. on malignant melanoma, interferon was applied to induce MHC class I and MHC class II molecules and as consequence levels of melanoma-specific CD4+ T lymphocytes increased [58,59]. Since MHC class II can be induced also on pancreatic cancer cells, an interferon-γ-based therapy is worth considering, especially in better differentiated cancers.…”

Trogocytosis Is a Gateway to Characterize Functional Diversity in Melanoma-Specific CD8+ T Cell Clones

“…Melanoma cell line M171 (HLA-A2 2 /MART-1 + ) was established in the Sharett Institute of Oncology, Hadassah Medical Organization (Jerusalem, Israel) (15). 624mel (HLA-A2 + /MART-1 + ) was a gift of M. Parkhurst (Surgery Branch, National Institutes of Health, Bethesda, MD).…”