Pro-tumorigenic functions of macrophages at the primary, invasive and metastatic tumor site

Abstract

The tumor microenvironment (TME) not only facilitates cancer progression from the early formation to distant metastasis, but also it differs itself from time to time alongside the tumor evolution. Tumor-associated macrophages (TAMs), whether as pre-existing tissue-resident macrophages or recruited monocytes, are an inseparable part of this microenvironment. As their parents are broadly classified into a dichotomic, simplistic M1 and M2 subtypes, TAMs also exert paradoxical and diverse phenotypes as they are settled in different regions of TME and receive different microenvironmental signals. Briefly, M1 macrophages induce an inflammatory precancerous niche and flame the early oncogenic mutations, whereas their M2 counterparts are reprogrammed to release various growth factors and providing an immunosuppressive state in TME as long as abetting hypoxic cancer cells to set up a new vasculature. Further, they mediate stromal micro-invasion and co-migrate with invasive cancer cells to invade the vascular wall and neural sheath, while another subtype of TAMs prepares suitable niches much earlier than metastatic cells arrive at the target tissues. Accordingly, at the neoplastic transformation, during the benign-to-malignant transition and through the metastatic cascade, macrophages are involved in shaping the primary, micro-invasive and pre-metastatic TMEs. Whether their behavioral plasticity is derived from distinct genotypes or is fueled by microenvironmental cues, it could define these cells as remarkably interesting therapeutic targets.

Development of a prognostic gene signature based on an immunogenomic infiltration analysis of osteosarcoma

“…This means that in our study the survival‐related immune cells impact the prognosis but not primarily by influencing metastasis and relapse. Metastasis and relapse are so complicated pathological processes in osteosarcoma that many experiments have illustrated the immune microenvironment takes part in 33,34 . We support that it will be more credible if the study samples were paired with metastasis or relapse lesions.…”

“…Metastasis and relapse are so complicated pathological processes in osteosarcoma that many experiments have illustrated the immune microenvironment takes part in. 33,34 We support that it will be more credible if the study samples were paired with metastasis or relapse lesions. In line with previous reviews, 17,35,36 poor necrosis stage (<90% necrosis) was potentially responsible for the poor overall survival of patients with osteosarcoma.…”

Lamin A/C and the Immune System: One Intermediate Filament, Many Faces

“…These cells take part in phagocytosis, inflammation, anti-pathogen responses, and tissue homeostasis [ 83 ]. Tissue-resident macrophages are present in all body tissues and may have their origin in the embryonic yolk sac, such as brain microglia, or in the fetal liver, such as lung alveolar macrophages and Kupffer cells in the liver [ 84 , 85 , 86 ]. Circulating monocytes originate in the bone marrow, and in the steady state these cells are usually found in blood, bone marrow, and spleen [ 87 ].…”

“…Circulating monocytes originate in the bone marrow, and in the steady state these cells are usually found in blood, bone marrow, and spleen [ 87 ]. Circulating monocytes are activated and recruited to tissues by several inflammation-induced chemotactic factors such as colony-stimulating factor-1 (CSF-1), chemokine (C-C motif) ligand (CCL)2, CCL5, chemokine (C-X3-C motif) ligand (CX3CL)1, chemokine (C-X-C motif) ligand (CXCL)12, growth factors like vascular endothelial growth factor (VEGF), and even extracellular components such as hyaluronic acid (HA) [ 86 ].…”

Hyaluronate-based Self-stabilized Nanoparticles for Reverting Immunosuppression and Immunochemotherapy in Osteosarcoma Treatment&nbsp;

“…Additionally, through the R848-mediated reeducation process, TAMs can be converted from a tumor-supportive phenotype to a tumoricidal phenotype. These tumoricidal TAMs can also enhance antitumor immunotherapy e cacy by releasing proin ammatory factors, inducing stromal destruction and normalizing the tumor vasculature [29,30]. Furthermore, the activated immune system can help the body systemically eliminate tumors and develop a speci c immune memory.…”