Circulating Tumor Cell-Neutrophil Tango along the Metastatic Process

• Published in: Cancer research (Chicago, Ill.) Vol. 79; no. 24; pp. 6067 - 6073
• Main Authors: Saini, Massimo, Szczerba, Barbara M, Aceto, Nicola
• Format: Journal Article
• Language: English
• Published: United States 15.12.2019
• Subjects: Animals; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Cell Communication - drug effects; Cell Communication - immunology; Costimulatory and Inhibitory T-Cell Receptors - antagonists & inhibitors; Costimulatory and Inhibitory T-Cell Receptors - immunology; Costimulatory and Inhibitory T-Cell Receptors - metabolism; Disease Models, Animal; Disease Progression; Humans; Neoplasm Metastasis - immunology; Neoplasm Metastasis - prevention & control; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Neoplastic Cells, Circulating - immunology; Neoplastic Cells, Circulating - metabolism; Neutrophil Infiltration; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-19-1972

The crosstalk between cancer cells and the immune system is crucial for disease progression and its therapeutic targeting is providing exciting results, in particular with newly developed immune checkpoint inhibitors. Current approaches primarily focus on cellular interactions occurring between tumor cells and T lymphocytes; however, recent data highlight a crucial role of neutrophils in support of tumor progression and suggest yet unexplored treatment opportunities. In this review, we summarize the current understanding of those interactions that occur between neutrophils and cancer cells, focusing on both protumor and antitumor activities of neutrophils at different stages of cancer progression. These include infiltration of neutrophils into the primary tumor, their interactions with circulating tumor cells (CTC) within the bloodstream, and their involvement in the establishment of a metastatic niche. Additionally, we discuss how further investigation of CTCs and their interacting immune cell partners may point towards novel immune checkpoint inhibition strategies and provide new insights on the efficacy of already existing immunotherapies.