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Impact of Tumor and Immunological Heterogeneity on the Anti-Cancer Immune Response.

ABSTRACT: Metastatic tumors are the primary cause of cancer-related mortality. In recent years, interest in the immunologic control of malignancy has helped establish escape from immunosurveillance as a critical requirement for incipient metastases. Our improved understanding of the immune system's interactions with cancer cells has led to major therapeutic advances but has also unraveled a previously unsuspected level of complexity. This review will discuss the vast spatial and functional heterogeneity in the tumor-infiltrating immune system, with particular focus on natural killer (NK) cells, as well as the impact of tumor cell-specific factors, such as secretome composition, receptor-ligand repertoire, and neoantigen diversity, which can further drive immunological heterogeneity. We emphasize how tumor and immunological heterogeneity may undermine the efficacy of T-cell directed immunotherapies and explore the potential of NK cells to be harnessed to circumvent these limitations.

PROVIDER: S-EPMC6770225 | BioStudies |

REPOSITORIES: biostudies

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