Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance.

Charita Furumaya,Panagiota Bouti,Paula Martinez-Sanz,Taco W Kuijpers,Hanke L Matlung

doi:10.3389/fimmu.2020.02100

Charita Furumaya, Panagiota Bouti + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2020.02100

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Abstract

Over the last decades, cancer immunotherapies such as checkpoint blockade and adoptive T cell transfer have been a game changer in many aspects and have improved the treatment for various malignancies considerably. Despite the clinical success of harnessing the adaptive immunity to combat the tumor, the benefits of immunotherapy are still limited to a subset of patients and cancer types. In recent years, neutrophils, the most abundant circulating leukocytes, have emerged as promising targets for anti-cancer therapies. Traditionally regarded as the first line of defense against infections, neutrophils are increasingly recognized as critical players during cancer progression. Evidence shows the functional plasticity of neutrophils in the tumor microenvironment, allowing neutrophils to exert either pro-tumor or anti-tumor effects. This review describes the tumor-promoting roles of neutrophils, focusing on their myeloid-derived suppressor cell activity, as well as their role in tumor elimination, exerted mainly via antibody-dependent cellular cytotoxicity. We will discuss potential approaches to therapeutically target neutrophils in cancer. These include strategies in humans to either silence the pro-tumor activity of neutrophils, or to activate or enhance their anti-tumor functions. Redirecting neutrophils seems a promising approach to harness innate immunity to improve treatment for cancer patients.

Highlights

The new immunotherapies aimed at targeting of immunosuppressive checkpoint receptors, using antibodies against the inhibitory programmed cell death protein 1 (PD-1)/programmed deathligand 1 (PD-L1) pathway or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathway, have vigorously changed the landscape of anti-cancer immunotherapy in the last decades [1]
We aim to provide a summary of the current knowledge and latest findings on pro- and anti-tumor activities of neutrophils by describing the main mechanisms of action and highlight some conceivable ways by which we could silence tumor-promoting activity or redirect the activity of pro-tumor neutrophils into cytotoxic effector cells to help combat cancer
The Fc region of the monoclonal antibody (mAb) can bind to activating Fc receptors on innate immune cells which will in turn elicit indirect-mediated killing via antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/P) of the opsonized cells [124,125,126,127,128]

Summary

Introduction

The new immunotherapies aimed at targeting of immunosuppressive checkpoint receptors, using antibodies against the inhibitory programmed cell death protein 1 (PD-1)/programmed deathligand 1 (PD-L1) pathway or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathway, have vigorously changed the landscape of anti-cancer immunotherapy in the last decades [1]. The Fc region of the mAb can bind to activating Fc receptors on innate immune cells which will in turn elicit indirect-mediated killing via antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/P) of the opsonized cells [124,125,126,127,128].

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