Tumor-associated macrophages and anti-tumor therapies: complex links

Belgiovine, Cristina; D’Incalci, Maurizio; Allavena, Paola; Frapolli, Roberta

doi:10.1007/s00018-016-2166-5

Cited by 107 publications

(100 citation statements)

References 173 publications

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“…Particularly, they promote tumor growth and dissemination, enhance angiogenesis, contribute to matrix degradation, and suppress anti‐tumor Th1‐mediated adaptive immunity (Chittezhath et al, ; Squadrito & De Palma, ). TAMs are major source of reactive mediators such as cytokines, chemokines, growth factors, ROS and RNS, and proteolytic enzymes (Belgiovine et al, ; Chittezhath et al, ). Pharmacological depletion of TAMs results in an inhibition of angiogenesis in tumors (Squadrito & De Palma, ).…”

Section: Macrophagementioning

confidence: 99%

Macrophage plasticity, polarization, and function in health and disease

Shapouri‐Moghaddam

Mohammadian

Vazini

et al. 2018

Journal Cellular Physiology

3,364

2,541

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Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1β, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.

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Section: Macrophagementioning

confidence: 99%

Macrophage plasticity, polarization, and function in health and disease

Shapouri‐Moghaddam

Mohammadian

Vazini

et al. 2018

Journal Cellular Physiology

3,364

2,541

View full text Add to dashboard Cite

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“…It is induced by myeloid regulatory cells such as neutrophils [212,213], TAM [214,215,216], MDSC [217,218,219,220], and regulatory DC [221,222]. In addition, Treg and carcinoma-associated fibroblasts (CAF) contribute to the immunosuppressive milieu [222,223,224,225].…”

Section: Role Of Il-1β In Tumor Developmentmentioning

confidence: 99%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

319

221

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Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

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Section: Cancer Niche: New Challengesmentioning

confidence: 99%

“…According to the literature, tumor associated macrophages (TAMs) are the major infiltrating leukocytes of the tumor micro-environment [62]. They have usually a M2-like phenotype and an immunosuppressive activity, producing growth factors for the tumor cells [62]. TAMs also promote dissemination of tumor cells enhancing angiogenesis and matrix degradation, suppressing Th1 immne ativity [63].…”

Section: Cancer Niche: New Challengesmentioning

confidence: 99%

Explaining the dynamics of tumor aggressiveness: At the crossroads between biology, artificial intelligence and complex systems

Porta

Zapperi

2018

Seminars in Cancer Biology

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Facing metastasis is the most pressing challenge of cancer research. In this review, we discuss recent advances in understanding phenotypic plasticity of cancer cells, highlighting the kinetics of cancer stem cell and the role of the epithelial mesenchymal transition for metastasis. It appears that the tumor micro-environment plays a crucial role in triggering phenotypic transitions, as we illustrate discussing the challenges posed by macrophages and cancer associated fibroblasts. To disentangle the complexity of environmentally induced phenotypic transitions, there is a growing need for novel advanced algorithms as those proposed in our recent work combining single cell data analysis and numerical simulations of gene regulatory networks. We conclude discussing recent developments in artificial intelligence and its applications to personalized cancer treatment.

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Tumor-associated macrophages and anti-tumor therapies: complex links

Cited by 107 publications

References 173 publications

Macrophage plasticity, polarization, and function in health and disease

Macrophage plasticity, polarization, and function in health and disease

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Explaining the dynamics of tumor aggressiveness: At the crossroads between biology, artificial intelligence and complex systems

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