The role and metabolic adaptations of neutrophils in premetastatic niches

Abstract

It has been found that tumor cells create microenvironments in distant organs that promote their survival and growth in advance of their arrival. These predetermined microenvironments are referred to as “pre-metastatic niches”. Increasing attention is being paid to neutrophils’ role in forming the pre-metastatic niche. As major components of the pre-metastatic niche, tumor-associated neutrophils (TANs) play an important role in the formation of the pre-metastatic niche through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together create a pre-metastatic niche well suited for tumor cell seeding and growth. However, how TANs modulate their metabolism to survive and exert their functions in the process of metastasis remains largely to be discovered. Accordingly, the objective of this review is to assess the role that neutrophils play in the formation of pre-metastatic niche and to explore the metabolism alteration of neutrophils in cancer metastasis. A better understanding of the role of TANs in pre-metastatic niche will help us discover new mechanisms of metastasis and develop new therapies targeting TANs.

Beyond the horizon: Neutrophils leading the way in the evolution of immunotherapy

“…It has been well established that the neutrophil chemokine axis CXCR4/CXCL12 is crucial in recruiting neutrophils to the pre‐metastatic niche such as in breast cancer, 60 and CXCL12 is upregulated in several different metastatic sites as reviewed by Chen and Yu. 61 This review reported illustrates the importance of the CXCR2‐dependent recruitment of neutrophils and the role of CXCL5 in promoting both recruitment of neutrophils to lymph nodes as well as lymph node metastasis. Furthermore, the stromal cell‐derived factor 1 (SDF1/CXCL12)‐CXCR4 axis also contributes to neutrophil recruitment to the liver pre‐metastatic niche.…”

Function and mechanism of exosomes derived from different cells as communication mediators in colorectal cancer metastasis

“…These predetermined microenvironments are commonly referred to as pre-metastatic niches. 11 , 105 Pre-metastatic niches are established through systemic signals emanating from the primary tumor prior to the arrival of cancer cells, which recruit supportive stromal cells and other cellular constituents. The perivascular microenvironment facilitates the extravasation of cancer cells and their dissemination along the basement membrane of capillaries.…”

“…Exosome-mediated intercellular communication plays a crucial role in various critical steps of metastatic colorectal cancer (mCRC) development and progression, including enhancing tumor cell invasion and migration capacity, altering vascular permeability, facilitating immune escape, and promoting pre-metastatic niche formation. 9 , 10 , 11 Exosomes also act as triggers or drivers for tumor metastasis occurrence when interacting with other factors. 6 , 12…”

Sustaining the Activation of EGFR Signal by Inflammatory Cytokine IL17A Prompts Cell Proliferation and EGFR-TKI Resistance in Lung Cancer

“…In addition to immune cells, some studies have suggested that tumor cells themselves might acquire the ability to produce IL-17A under certain conditions or in specific types of tumors. For example, colorectal and breast cancers are capable of producing IL-17 to guide IL-17R-positive neutrophils’ directional migration [ 5 ]. IL-17A targets various cells which contain its receptor, composed of IL-17RA and IL-17RC dimers, which results in host defense, chronic inflammation, tissue destruction and repair, and oncogenesis [ 6 , 7 ].…”