NK cells and solid tumors: therapeutic potential and persisting obstacles

Abstract

Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity.

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

“…To further verify these associations, we adopted another algorithm, CIBERSORT, to assess the abundance of 22 immune components. In most cancers, CAFs had a negative correlation with CD8+ T cells and activated NK cells, both of which are well‐known for their anti‐tumor functions 65,66 . Conversely, M0 and M2 macrophages showed positive correlation with CAFs in most cancers (Figure 2E).…”

“…In most cancers, CAFs had a negative correlation with CD8+ T cells and activated NK cells, both of which are wellknown for their anti-tumor functions. 65,66 Conversely, M0 and M2 macrophages showed positive correlation with CAFs in most cancers (Figure 2E). These results indicated that CAFs could recruit tumor-promoting immune cells, while excluding anti-tumor cells, further remodelling the TME and promoting tumor progression.…”

The Characteristics of Natural Killer Cells and Prediction of Prognosis in Bladder Urothelial Carcinoma

“…After consulting the literature, we learned that whether the function of NK cells can work is closely related to cell metabolism functions, such as cell hypoxia, energy supply, amino acid cycle, etc [33,34] . FasL-related GTP-related signal pathway is also involved [35] . The results and enrichment results corroborated with each other.…”

Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond

“…Notably, the induction of a memory-like phenotype using IL-2, IL-15, and IL-18 holds great potential in improving both the cytotoxicity and persistence of NK cells [69]. To date, the most prominent success in NK cell adoptive transfer has been with IL-15-enhanced CAR-NK products against CD19-expressing lymphomas, while progress in other hematologic malignancies and solid tumor targets remain in earlier investigational stages [6,181,185]. Nonetheless, the recent advances in NK cell therapies and other methods in leveraging NK cell cytotoxicity have demonstrated the great promise of this cellular therapy platform.…”