Natural killer (NK) cells are a population of innate lymphoid cells playing a pivotal role in host immune responses against infection and tumor growth. These cells have a powerful cytotoxic activity orchestrated by an intricate network of inhibitory and activating signals. The importance of NK cells in controlling tumor growth and in mediating a robust anti-metastatic effect has been demonstrated in different experimental mouse cancer models. Consistently, high density of tumor-infiltrating NK cells has been linked with a good prognosis in multiple human solid tumors. However, there are also tumors that appear to be refractory to NK cell-mediated killing for the presence of an immunosuppressive microenvironment affecting NK cell function. Immunotherapeutic strategies aimed at restoring and increasing the cytotoxic activity of NK cells in solid tumors, including the adoptive transfer of NK and CAR-NK cells, are currently employed in preclinical and clinical studies. In this review, we outline recent advances supporting the direct role of NK cells in controlling expansion of solid tumors and their prognostic value in human cancers. We summarize the mechanisms adopted by cancer cells and the tumor microenvironment to affect NK cell function, and finally we evaluate current strategies to augment the antitumor function of NK cells for the treatment of solid tumors.

Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors / Melaiu, Ombretta; Lucarini, Valeria; Cifaldi, Loredana; Fruci, Doriana. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 10:(2019), p. 3038. [10.3389/fimmu.2019.03038]

Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors

Lucarini, Valeria;Cifaldi, Loredana;
2019

Abstract

Natural killer (NK) cells are a population of innate lymphoid cells playing a pivotal role in host immune responses against infection and tumor growth. These cells have a powerful cytotoxic activity orchestrated by an intricate network of inhibitory and activating signals. The importance of NK cells in controlling tumor growth and in mediating a robust anti-metastatic effect has been demonstrated in different experimental mouse cancer models. Consistently, high density of tumor-infiltrating NK cells has been linked with a good prognosis in multiple human solid tumors. However, there are also tumors that appear to be refractory to NK cell-mediated killing for the presence of an immunosuppressive microenvironment affecting NK cell function. Immunotherapeutic strategies aimed at restoring and increasing the cytotoxic activity of NK cells in solid tumors, including the adoptive transfer of NK and CAR-NK cells, are currently employed in preclinical and clinical studies. In this review, we outline recent advances supporting the direct role of NK cells in controlling expansion of solid tumors and their prognostic value in human cancers. We summarize the mechanisms adopted by cancer cells and the tumor microenvironment to affect NK cell function, and finally we evaluate current strategies to augment the antitumor function of NK cells for the treatment of solid tumors.
2019
adoptive transfer of NK and CAR-NK cells; cancer stem cells; cellular metabolism; hypoxia; immune checkpoint inhibitors; natural killer cells; solid tumors; tumor microenvironment
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors / Melaiu, Ombretta; Lucarini, Valeria; Cifaldi, Loredana; Fruci, Doriana. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 10:(2019), p. 3038. [10.3389/fimmu.2019.03038]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1700289
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 169
  • Scopus 241
  • ???jsp.display-item.citation.isi??? 228
social impact