The tumor immune microenvironment (TIME) is comprised of a complex milieu that contributes to stunting antitumor immune responses by restricting T cells to accumulate in the vicinity of the tumor. Nanomedicine-based strategies are being proposed as a salvage effort to reinvigorate antitumor immunity. Various strategies, however, often fail to unleash the antitumor immune response because of the paucity of appropriate therapeutic targets in the complex TIME, invigorating a fervor of investigation into mechanisms underlying the TIME to resist nanomedicines. In this review article, effective nano/biomaterial-based delivery and TIME normalization approaches that promote T cell-mediated antitumor immune response will be discussed, with a focus on emerging preclinical and clinical strategies for immune normalization. Based on currently available evidence, it seems as if the ultimate success of cancer immunotherapy and nanomedicine hinges on the capacity to normalize the TIME. Here, how nanomedicines target immunosuppressive cells and signaling pathways to broaden the impact of cancer immunotherapy are explored. Acquisition of the urgently needed knowledge of nanomedicine-mediated immune normalization will guide researchers and scientists towards clinical applications of cancer immunotherapy.
Keywords: clinical translation; nanobiomaterials; nanovaccines; normalization cancer immunotherapy; primary and adaptive resistance; tumor immune microenvironment.
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