Partners in Crime: Neutrophil-CTC Collusion in Metastasis

Abstract

A recent study in Nature (Szczerba et al. 2019;566:553-557) reports that the association of neutrophils with circulating tumor cells (CTCs) in the blood of patients with breast cancer can promote CTC proliferation and metastasis. These findings reveal a new mechanism by which the innate immune system may be co-opted to drive tumor progression.

Figure 1. Circulating Tumor Cell (CTC)–Neutrophil Clusters Can Have Increased Metastatic Potential in Breast Cancer.

CTCs are shed from primary breast tumor sites and travel through the bloodstream mostly as single CTCs, but some can be detected as CTC clusters or CTC–neutrophil clusters in mice and humans. Relative to CTC clusters or single CTCs, CTCs from neutrophil clusters exhibit increased proliferation that may be driven, in part, by cytokines such as interleukin (IL)6 and IL1B, expressed by neutrophils. CTCs from neutrophil clusters also exhibit an enhanced ability to promote metastases in multiple mouse tumor models. Genetic and pharmacological inhibition of distinct steps of this cascade, such as vascular cell adhesion molecule 1 (VCAM1), lymphocyte antigen 6 complex, locus G (LY6G) or C-X-C motif chemokine receptor 2 (CXCR2) blockade might bear potential in suppressing tumor metastasis.