Fig. 5

Mechanisms of interferon-γ mediated cancer promotion. Tumor metastasis may be facilitated by IFN-γ which induces the expression of ICAM1 and CD13, EMT or CXCR4 and the production of MUC4. Combination of anti-CTLA-4-antibody and anti-PD(L)-1-antibody may highly stimulate secretion of IFN-γ in the TME, which in turn results in CD8+ T-cell apoptosis. The IFN-γ increases synthesis of inhibitory molecules, IDO, and PD-L1, and induces genome immunoediting. High IFN-γ-stimulated PD-L1 expression on lymphatic endothelial cells prevent CTL’s migration to the TME and thus, damps immune response. EMT-epithelial–mesenchymal transition; ICAM1-intercellular adhesion molecule 1; CXCR4-C-X-C chemokine receptor type 4; MUC4-mucin 4; CTL-cytotoxic T lymphocytes