The roles of tissue resident macrophages in health and cancer

Abstract

As integral components of the immune microenvironment, tissue resident macrophages (TRMs) represent a self-renewing and long-lived cell population that plays crucial roles in maintaining homeostasis, promoting tissue remodeling after damage, defending against inflammation and even orchestrating cancer progression. However, the exact functions and roles of TRMs in cancer are not yet well understood. TRMs exhibit either pro-tumorigenic or anti-tumorigenic effects by engaging in phagocytosis and secreting diverse cytokines, chemokines, and growth factors to modulate the adaptive immune system. The life-span, turnover kinetics and monocyte replenishment of TRMs vary among different organs, adding to the complexity and controversial findings in TRMs studies. Considering the complexity of tissue associated macrophage origin, macrophages targeting strategy of each ontogeny should be carefully evaluated. Consequently, acquiring a comprehensive understanding of TRMs' origin, function, homeostasis, characteristics, and their roles in cancer for each specific organ holds significant research value. In this review, we aim to provide an outline of homeostasis and characteristics of resident macrophages in the lung, liver, brain, skin and intestinal, as well as their roles in modulating primary and metastatic cancer, which may inform and serve the future design of targeted therapies.

Macrophage Functions in Psoriasis: Lessons from Mouse Models

“…Skin-resident macrophages can be classified into two main subtypes, i.e., Langerhans cells (LCs) of the epidermis and dermal macrophages [6]. Due to their mixed origin, LCs share the features of both macrophages and dendritic cells [7].…”

“…Due to their mixed origin, LCs share the features of both macrophages and dendritic cells [7]. Therefore, they are capable of presenting antigens to T lymphocytes in the skin and draining lymph nodes [6]. At the immunological synapse, LC-derived signaling enables T cells to adapt the effector immune response to the type of antigenic stimulus [8].…”

Function of alveolar macrophages in lung cancer microenvironment

“…AMs, together with the alveolar epithelium, play a central role in protecting against the outside environment and are closely linked to the alveolar epithelium. AMs are conjunct to alveolar epithelial cells and receive granulocyte–macrophage colony-stimulating factor (GM-CSF) from epithelial cells [ 8 , 15 ]. GM-CSF, encoded by the colony-stimulating factor 2 ( Csf2 ) gene, is necessary for the differentiation of fetal monocytes into AMs, and macrophages found in the airways of Csf2 knockout (KO) mice cannot fully differentiate into AMs [ 16 ].…”

“…These findings suggest that cancer tissues contain TRMs in addition to infiltrating macrophages or TAMs. However, although previous studies have reported the interactions between some TRMs and malignant tumors such as glioma, hepatocellular carcinoma, and metastatic cancer, the exact functions and roles of TRMs in cancer tissues are not fully understood [ 8 – 10 ].…”