Figures & data
Figure 1. CD40-based combination immunotherapy restructures the tumor microenvironment. Tumor-promoting immunoregulatory cells often prevail within the tumor microenvironment (upper half). These cells contribute to tumor growth, angiogenesis and immunosuppression through the expression of immunoregulatory cytokines as well as chemokines responsible for regulatory T cell (Treg) and myeloid-derived suppressor cell (MDSC) recruitment. Tumor-associated Fas ligand expression under normal conditions may contribute to tumor escape by eliciting death of Fas-ligand positive effector T cells. After treatment with anti-CD40 agonistic antibody in combination with IL-2, IL-15 or the mTOR-kinase inhibitor AZD8055 (bottom half) therapy, the tumor environment is converted into one in which T helper type 1 (Th1) cytokines and effector immune cells predominate. These cells mediate apoptosis of Tregs and MDSCs, and drive malignant cell killing, therebyreducing tumor metastatic potential. IFNγ, interferon γ; NK, natural killer; NO, nitric oxide, TGFβ, transforming growth factor β; VEGF, vascular endothelial growth factor.
