Neutrophil diversity and plasticity in tumour progression and therapy

Abstract

Neutrophils play a key role in defence against infection and in the activation and regulation of innate and adaptive immunity. In cancer, tumour-associated neutrophils (TANs) have emerged as an important component of the tumour microenvironment. Here they can exert dual functions. TANs can be part of tumour-promoting inflammation by driving angiogenesis, extracellular matrix remodelling, metastasis and immunosuppression. On the other hand, neutrophils can mediate antitumour responses by direct killing of tumour cells and by participating in cellular networks that mediate anti-tumour resistance. Neutrophil diversity and plasticity underlie the dual potential of TANs in the tumour microenvironment. Myeloid checkpoints as well as the tumour and tissue contexture shape neutrophil function in response to conventional therapies and immunotherapy. We surmise that neutrophils can provide tools to tailor current immunotherapy strategies and pave the way to myeloid cell-centred therapeutic strategies complementary to current approaches.

The complexity of neutrophils in health and disease: Focus on cancer

“…In steady state, both circulating and tissue neutrophils are endowed with functional and phenotypic characteristics [ 16 , 116 ]. Accordingly, neutrophil heterogeneity has been associated with different parameters, such as maturation, ageing or activation states in response to signals from the tissue microenvironment, such as cytokines [ 19 ].…”

“…The role of neutrophils in tumour biology has long been underestimated while particular emphasis has been placed on the role of other myeloid cells, such as macrophages [ 12 , 13 ]. However, recent findings showed that neutrophils are an important component of the TME and have highlighted their importance in tumour progression as well as in the orchestration of pathways leading to tumour resistance [ [14] , [15] , [16] , [17] , [18] ]. These contrasting findings are likely the results of the previously underestimated plasticity and heterogeneity of neutrophils in cancer [ 8 , 16 , 19 ].…”

“…However, recent findings showed that neutrophils are an important component of the TME and have highlighted their importance in tumour progression as well as in the orchestration of pathways leading to tumour resistance [ [14] , [15] , [16] , [17] , [18] ]. These contrasting findings are likely the results of the previously underestimated plasticity and heterogeneity of neutrophils in cancer [ 8 , 16 , 19 ]. In humans, the density of tumour-associated neutrophils (TANs) can have prognostic significance for patient’s outcome [ [20] , [21] , [22] , [23] ].…”

The Novel Ferroptosis-related Gene Markers That Can Predict the Survival in Gastric Cancer Patients

“…Neutrophils are well known in infections of the organism. In tumors, tumor-associated neutrophils can induce angiogenesis, ECM remodeling, metastasis, and immunosuppression [37] . The function of these immune cells in the tumor microenvironment allows us to speculate whether the cells release special signals during the ferroptosis, so that mast cells and neutrophils promote angiogenesis and further promote the proliferation metastasis of tumor cells.…”

Technical Advancements for Studying Immune Regulation of Disseminated Dormant Cancer Cells

“…Neutrophils represent another abundant component of innate immunity whose contribution in cancer has only started to be elucidated in the last few years ( 108 ). Neutrophils have been shown to boost lung metastasis from breast cancer ( 81 , 109 – 111 ) and to reawaken DDCCs ( 41 , 107 ).…”