Fig. 3. Tumor hypoxia and acidosis promote immunosuppression.

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Fig. 3. Tumor hypoxia and acidosis promote immunosuppression. Tumor hypoxia and acidosis promote immunosuppression. AngII/AT1R-mediated effects on tumor vasculature (shown in Fig. 2) can impair tumor perfusion and oxygenation, resulting in hypoxia and acidosis within the tumor stroma. The resulting up-regulation of various cytokines, growth factors, and transcription factors [including HIF (hypoxia-inducible factor), VEGF, and TGF-β] enhances an immunosuppressive microenvironment, characterized by impaired T and dendritic cell function, accumulation of immunosuppressive cell types (M2-like macrophages, MDSCs, and Tregs), and increased expression of inhibitory immune checkpoint molecules such as PD-L1 in tumor and immune cell types (48–50, 68). Ang-2, angiopoietin-2; CCL, CC chemokine ligand; CTLA-4, cytotoxic T lymphocyte–associated protein 4; SDF, stromal cell–derived factor. Matthias Pinter and Rakesh K. Jain Sci Transl Med 2017;9:eaan5616 Published by AAAS