Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer

Abstract

Monocytes and their tissue counterpart macrophages (MP) constitute the front line of the immune system. Indeed, they are able to rapidly and efficiently detect both external and internal danger signals, thereby activating the immune system to eradicate the disturbing biological, chemical, or physical agents. They are also in charge of the control of the immune response and account for the repair of the damaged tissues, eventually restoring tissue homeostasis. The balance between these dual activities must be thoroughly controlled in space and time. Any sustained unbalanced response of MP leads to pathological disorders, such as chronic inflammation, or favors cancer development and progression. In this review, we take advantage of our expertise in chronic inflammation, especially in rheumatoid arthritis, and in cancer, to highlight the pivotal role of MP in the physiopathology of these disorders and to emphasize the repolarization of unbalanced MP as a promising therapeutic strategy to control these diseases.

The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis

“…Macrophages were described for the first time in 1882 by Metchnikov as the “big eater” of the immune system and represent the frontier soldiers of immune system, thanks to their capability to recognize, engulf, and destroy pathogens through the activation of TLRs and the production of pro- and anti-inflammatory mediators ( 33 , 34 ).…”

“…Moreover, the expression of TLR4 on macrophages permits to recognize endogenous ligands relevant in RA, such as native articular proteins and citrullinated peptides, and subsequently induces intracellular signal transduction finalized to a prompt expression of pro-inflammatory genes through the activation of nuclear factor kappa B (NF-kB) signaling pathway ( 33 , 45 ): in fact, the activation of TLR4-induced NF-kB signaling pathway mediates the pro-inflammatory activity of M1 macrophages through the production and release of IL-6, TNFα, and IL-1β in monocyte-derived and synovial macrophages obtained from RA patients ( Figure 3 ) ( 46 , 47 ).…”

Liposomal AntagomiR‐155‐5p Restores Anti‐Inflammatory Macrophages and Improves Arthritis in Preclinical Models of Rheumatoid Arthritis

“…Monocytes and macrophages are key players in the pathogenesis and therapeutic response in rheumatoid arthritis (RA). [1][2][3][4][5] A number of studies have found an increase of pro-inflammatory macrophage recruitment and activation in synovium in both human and mouse models. 4,[6][7][8] On the other hand, the overexpression of some microRNAs (miRs) associated with inflammation has been detected in the blood and synovium of patients with RA.…”

The prognostic value of systemic immune-inflammation index in surgical esophageal cancer patients: An updated meta-analysis

“…In recent years, a lot of studies have demonstrated that systemic inflammation plays an essential role in the incidence and development of cancers (6)(7)(8)(9). Furthermore, several inflammatory biomarkers have been manifested to show relatively high prognostic value in esophageal cancer such as the neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), and C-reactive protein to albumin ratio (CAR) (10)(11)(12)(13)(14).…”