Natural killer (NK) cells are innate immune cells with cytotoxic potentials to kill cancerous cells in several mechanisms, which could be implied for cancer therapy. While potent, their antitumor activities specially for solid tumors impaired by inadequate tumor infiltration, suppressive tumor microenvironment, cancer-associated stroma cells, and tumor-supportive immune cells. Therefore, manipulating or reprogramming these barriers by prospective strategies might improve current immunotherapies in the clinic or introduce novel NK-based immunotherapies. NK-based immunotherapy could be developed in monotherapy or in combination with other therapeutic regimens such as oncolytic virus therapy and immune checkpoint blockade, as presented in this review.
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