Macrophages and Natural Killer cells (Mφ and NK cells)

Macrophages and Natural Killer (NK) cells are essential components of the innate immune system, serving as the first line of defense against pathogens and malignant cells (StatPearls, 2023). Macrophages are versatile phagocytes that clear debris, present antigens to the adaptive immune system, and regulate tissue repair and inflammation through various polarization states, such as the pro-inflammatory M1 or anti-inflammatory M2 phenotypes (NCBI, 2022). Natural Killer cells are specialized cytotoxic lymphocytes that recognize and destroy stressed, infected, or cancerous cells by detecting the absence of MHC class I molecules or the presence of stress-induced ligands (Frontiers in Immunology, 2021). In therapeutic development, these cells are often the focus of immunotherapies designed to enhance their anti-tumor activity, such as through the use of checkpoint inhibitors, bispecific antibodies, or chimeric antigen receptor (CAR) technologies (Journal of Hematology & Oncology, 2021). Drugs like pexidartinib target macrophage receptors to reduce immunosuppression, while monoclonal antibodies like rituximab utilize NK cells to execute antibody-dependent cellular cytotoxicity (ADCC) (Nature Reviews Drug Discovery, 2020). However, because they are complex cellular populations rather than single molecular entities, they are generally categorized as cellular effectors or components of the microenvironment rather than individual therapeutic targets. Their dysregulation is a hallmark of various pathologies, including chronic inflammatory diseases and the formation of an immunosuppressive tumor microenvironment (Cell, 2020). Therapeutic strategies often aim to either deplete suppressive macrophage subsets or activate NK cell-mediated killing to restore immune surveillance.

Other names

Monocyte-derived macrophagesLarge granular lymphocytesTumor-associated macrophagesNK cells

Modulation of immune cell activity, recruitment, or polarization; antibody-dependent cellular cytotoxicity (ADCC); phagocytosis enhancement.