Natural Killer Cells and Myeloid Cells in Tumor Microenvironment: How to Enhance Their Anti-tumor Activity?

Dear Colleagues,

It is well-known that natural killer (NK) cells are the cytotoxic members of the innate lymphoid family. Due to their expression of an array of activating surface receptors and potent cytolytic machinery, NK cells have the potential to efficiently recognize and kill most tumor cells. However, experimental data and clinical evidence have revealed that the predicted efficacy of these cells may be severely impaired in vivo through the influences of several factors affecting their recruitment, persistence, and activation at the tumor site. The tumor microenvironment (TME) contains several immune effectors, including tumor-associated macrophages and neutrophils, myeloid-derived suppressor cells, cancer-associated fibroblasts, and regulatory T cells capable of modulating the function of NK cells, thus disabling their anti-tumor efficacy. This effect can occur through both cell-to-cell contact and the release of factors that are also carried by extracellular vesicles, such as exosomes. Moreover, TME metabolic features, such as hypoxia, high levels of adenosine, reactive oxygen species, and prostaglandins negatively affect the activity of NK cells. Finally, more recent methodological approaches have revealed a heterogeneity of the NK cell population that is much higher than that originally described and includes circulating or resident cells possessing different phenotypic and functional characteristics.

Although the exploitation of NK cell functions has demonstrated encouraging fallouts in hematological malignancies, the results obtained from experiments conducted on solid tumors are disappointing. The identification of the barriers constructed by tumors or by tumor-associated myeloid cells, which affect the NK anti-tumor response, and the definition of potential strategies that may be used to circumvent such obstacles remain crucial challenges in our efforts to improve the clinical outcomes of cancer patients.

We welcome original articles, reviews, minireviews, and commentaries with aim of collecting new information and fostering critical discussion regarding the activity of NK cells and myeloid cells in the tumor microenvironment.

Prof. Roberta Castriconi
Prof. Cristina Bottino
Guest Editors

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• NK, natural killer
• myeloid cells
• innate lymphoid family
• tumor microenvironment