Figure 1

Optimal MHC-II-restricted tumor antigen presentation as a key parameter for an effective anti-tumor adaptive immune response. Optimal MHC-II-restricted tumor antigen presentation may result from either surrogate antigen presenting activity by tumor cells expressing CIITA-dependent MHC class II (MHC-II) molecules or by increasing the amount of tumor antigen availability for classical antigen-presenting cells (APC) via therapeutical approaches resulting in immunogenic cell death, such as radiotherapy (RT), chemotherapy, and biotherapy with, for example, L19-TNFα and melphalan (L19-TNFα + Melphalan). Optimal MHC-II-restricted tumor antigen presentation generated by the two approaches is instrumental for the optimal triggering of anti-tumor CD4+ T helper cells (TH). These MHC-II-restricted anti-tumor TH cells have a dual action in the process of immune-mediated tumor rejection: a) they are required for the activation, proliferation and cytolytic activity of CD8+ anti-tumor cytotoxic T lymphocytes (CTL); b) they are major players in the subversion of the tumor microenvironment toward an anti-tumor milieu by polarizing, for example, the lymphocyte infiltrate toward a mixed TH1/TH2 or exclusive TH1 population with an increased frequency of IFNγ secreting cells, by favouring the recruitment of inflammatory cells such as polymorphonuclear cells, by inhibiting the function and/or the recruitment of leukocytes with suppressive action on TH cells and on tumor-specific CTL.