Tumor microenvironment: Nurturing cancer cells for immunoevasion and druggable vulnerabilities for cancer immunotherapy.

The tumor microenvironment (TME) is an intricate ecosystem where cancer cells thrive, encompassing a wide array of cellular and non-cellular components. The TME co-evolves with tumor progression in a spatially and temporally dynamic manner, which endows cancer cells with the adaptive capability of evading immune surveillance. To this end, diverse cancer-intrinsic mechanisms were exploited to dampen host immune system, such as upregulating immune checkpoints, impairing antigens presentation and competing for nutrients. In this review, we discuss how cancer immunoevasion is tightly regulated by hypoxia, one of the hallmark biochemical features of the TME. Moreover, we comprehensively summarize how immune evasiveness of cancer cells is facilitated by the extracellular matrix, as well as soluble components of TME, including inflammatory factors, lactate, nutrients and extracellular vesicles. Given their important roles in dictating cancer immunoevasion, various strategies to target TME components are proposed, which holds promising translational potential in developing novel therapeutics to sensitize anti-cancer immunotherapy such as immune checkpoint blockade.