Interferon-alpha (IFN-α) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC)

Abstract

SUMMARYIFN-a administration after primary tumour resection improves the survival of melanoma patients at high risk of relapse. To investigate whether this response might be due to stimulation of anti-tumour immunity, the effect of IFN-a on anti-melanoma CTL generation in MLTC was measured. IFN-a increased both allogeneic and autologous anti-melanoma CTL generation from peripheral blood lymphocytes stimulated with irradiated primary melanoma cultures. IFN-a up-regulated MHC class I expression on primary melanoma cultures, whereas IFN-g up-regulated both MHC class I and II expression. However, the effect of IFN-a on anti-melanoma CTL generation was often more potent than that of IFN-g , equalling the effect of the optimal combination of IL-2 and IL-12. Pre-treatment of primary melanoma cultures with IFN-g was sufficient for CTL generation in MLTC, whereas IFN-a needed to be present during the MLTC. While direct anti-proliferative effects of IFN-a on some tumour cells have been described, IFN-a did not inhibit proliferation of primary melanoma cultures. These results suggest that the clinical effects of IFN-a in melanoma patients may be immune-mediated.

Type I IFN as a Natural Adjuvant for a Protective Immune Response: Lessons from the Influenza Vaccine Model

“…For a long time, the importance of the effects of type I IFN on the immune system remained poorly considered (6). In recent years, however, some reports have shown that these cytokines affect the differentiation, survival, and function of immune cells, including T cells (7)(8)(9)(10)(11)(12)(13)(14)(15) and dendritic cells (DCs) 3 (16 -20) and efficiently enhance a primary Ab response (21). In a recent study it was shown that immunization of mice with chicken ␥-globulin in the presence of type I IFN results in the generation of a potent primary immune response, characterized by an isotype switching toward IgG2a Abs (21).…”

Amelanotic lentigo maligna managed with topical imiquimod as immunotherapy

“…41 It has been shown to stimulate anti-melanoma cytotoxic T lymphocytes in melanoma cell cultures. 42 Systemic IFN-␣ has been shown to improve disease-free and overall survival in advanced melanoma, 43 and intralesional IFN-␣ as therapy has been reported in melanoma 44 and in both LM and recurrent LM. 45 The successful use of topical imiquimod in the treatment of cutaneous neoplasia is presumably brought about by its ability to act as a potent apoptosis inducer and immune response-modifying agent through the induction of IFN-␣ and other cytokines.…”

Activation of Tumor Antigen-Specific Cytotoxic T Lymphocytes (CTLs) by Human Dendritic Cells Infected with an Attenuated Influenza A Virus Expressing a CTL Epitope Derived from the HER-2/neu Proto-Oncogene

“…PBMC priming was associated with expansion of E75 ϩ TCR cells (more than 10-fold) and induction of E75 (21) due to a decrease in NS1 dimerization that partly impairs the ability of the NS1 to prevent IFN-␣/␤ synthesis in infected cells (49). Taking into consideration the recently reported effects of IFN-␣ on the induction of survival and maturation of CTLs (22,37), the use of vectors based on rIVs with truncated NS1 proteins may be a promising strategy for human cancer vaccination. CTLs induced by KIF-NS DCs specifically recognized the E75 peptide presented by HLA-A2 ϩ cells in cytokine assays.…”