Neutrophils as immune effector cells in antibody therapy in cancer

Abstract

Over the last decades, new therapies have greatly improved the treatment of different cancer types. For example, immunotherapy is the collective of therapies that aims to recruit and stimulate the patient's own immune system to eradicate the tumor. 1 The tumor microenvironment (TME) comprises a great variety of cells, including endothelial cells, fibroblasts, and immune cells. Immune cells in the TME play a crucial role during cancer progression. Via immunosurveillance, immune cells are able to identify and eliminate malignant cells in the early stages. 2 However, certain mutations may cause adaptations that allow tumor cells to go undetected, for example, by downregulating MHC molecules. In addition, tumor cells may upregulate immunosuppressive molecules or secrete immunosuppressive cytokines to resist immune-mediated destruction. [3][4][5] Recruitment of immunosuppressive cells to the TME further polarizes the TME to an anti-inflammatory environment that prevents tumor killing and promotes disease progression. 6,7 Various types of agents to promote the immune system to eliminate tumor cells are in development or have become the standard of care in the treatment of cancer patients. This includes monoclonal antibodies (mAbs), adoptive (CAR) T cell transfer, or dendritic cell (DC) vaccination. Monoclonal antibodies include checkpoint inhibitors as well as tumor-associated antigen (TAA)-targeting antibodies directed against membrane components

STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy

“…43 We also observed polymer-diABZI uptake by DCs, professional antigen presenting cells that can prime antitumor T cell responses, as well as granulocytes that may also promote antitumor immunity in response to STING activation (Figure 4F-H, S14). 44,45,46 Consistent with their relatively poor capacity for endocytosis, we did not observe uptake by T cells; this may reflect an additional advantage of SAPCon over free diABZI since T cells are susceptible to STING-induced apoptosis.…”

IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma

“…Additionally, GO and KEGG gene enrichment analyses suggested that IMPDH1 was associated with neutrophil-related innate immunity and FC gamma R mediated phagocytosis in HCC. As innate immune cells, neutrophils promotes tumor progression by regulating the expression of various inflammatory factors and influencing phagocytosis ( 53 ). Targeting or manipulating neutrophils may gain clinical benefits and are expected to be combined with immunotherapy ( 54 , 55 ).…”

Neutrophils and their friends

“…The ability to harness the activity of neutrophils to halt tumor progression, promote elimination of cancer cells, or both could provide clinicians with potent therapies with fewer toxicities than those associated with current interventions. Behrens et al 17…”

“…The ability to harness the activity of neutrophils to halt tumor progression, promote elimination of cancer cells, or both could provide clinicians with potent therapies with fewer toxicities than those associated with current interventions. Behrens et al 17 review how neutrophils and monoclonal antibodies can support antibody‐directed cellular cytotoxicity. With tumor cells covered by tumor‐specific monoclonal antibodies, neutrophils can drive tumor killing.…”

“…Critical for this intervention to yield results is formation of the neutrophil cytotoxic synapse: a tight cellular structure dependent on conformational changes that follow binding by Mac‐1 (aka complement receptor 3, α m β 2 , CD11b CD18). Firmly associated with antibody‐targeted tumor cells, neutrophils exert tumor cytotoxicity in a variety of different ways, including trogocytosis, as discussed in detail 17 …”