Abstract
The efficacy of natural killer (NK) cell-based therapies against solid tumors has been poor. Solid tumors generate a hostile tumor microenvironment (TME) comprising multiple cell types including inhibitory immune cells that play a key role in depressing the antitumor functions of therapeutic NK cells. Understanding how inhibitory immune effectors operate within the confines of the TME is critical to developing therapies to reverse this inhibition. In this chapter, we cover the suppressive mechanisms employed by TME-resident inhibitory immune cells and discuss methodologies to assess their composition and functionality within the TME. We also highlight novel therapeutic strategies that target inhibitory cells of the TME to improve the antitumor functions of endogenous or adoptively transferred NK cells. Multimodal approaches to overcome inhibitory immune cells within the TME will drive the development of personalized NK cell therapeutics with optimal activity, leading to improved clinical outcomes in patients with solid tumors.
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