TAM macrophages promote growth and metastasis within the cancer ecosystem

Zarif, Jelani C.; Taichman, Russell S.; Pienta, Kenneth J.

doi:10.4161/21624011.2014.941734

Cited by 30 publications

(21 citation statements)

References 11 publications

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“…45 Also, CCL2 and CXCL1 regulate the polarization of M1 macrophages to M2 phenotype and the recruitment of TAMs to tumor microenvironment. [46][47][48] The reduction of CCL2 and CXCL1 may support LAG-3 could impact the chemokine governing MDSCs and TAMs accumulation. Consistently, the blockade of LAG-3 results in pDC activation while reducing the level of CCL2 with subsequent limitation of MDSCs population.…”

Section: And Cd11bmentioning

confidence: 97%

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

et al. 2016

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Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint control protein that negatively regulates T cells and immune response. Here, using the human tissue samples, we report these findings that LAG-3 is overexpressed on tumorinfiltrating lymphocytes (TILs; p < 0.001) and its overexpression correlates with the high pathological grades, lager tumor size and positive lymph node status in human primary HNSCC. Survival analysis identifies LAG-3 as a prognostic factor independent of tumor size and pathological grades for primary HNSCC patients with negative lymph node status (p D 0.014). Study in immunocompetent genetically defined HNSCC mouse model reports that LAG-3 is upregulated on CD4 C T cells, CD8 C T cells and CD4 C Foxp3 C regulatory T cells (Tregs). In vivo study, administration of LAG-3-specific antibody retards tumor growth in a way associated with enhanced systemic antitumor response by potentiating the antitumor response of CD8 C T cells and decreasing the population of immunosuppressive cells. Taken together, our results offer a preclinical proof supporting the immunomodulatory effects of LAG-3 and suggest a potential therapeutic target of immunotherapy for HNSCC.

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Section: And Cd11bmentioning

confidence: 97%

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

et al. 2016

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“…Tissue resident macrophages (TRMs) are phagocytic immune cells that also contribute to organogenesis and tissue homeostasis. Therefore, perturbations in TRM production or activity can have detrimental consequences ranging from abnormal organ development to neurodegeneration and cancer (Cassetta and Pollard, 2018; Mass et al, 2017; Yang et al, 2018; Zarif et al, 2014). In vertebrates, including mammals, birds, and fishes, TRMs derive from successive waves of hematopoiesis that initiate early during development (reviewed in: (McGrath et al, 2015)).…”

Section: Introductionmentioning

confidence: 99%

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Kuil

Oosterhof

Ferrero

et al. 2020

Preprint

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20Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages 21 require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the 22 absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-23 deficient zebrafish and report that embryonic macrophages emerge followed by their 24 developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct 25 types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, 26 although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were 27 present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. 28They expressed macrophage-associated genes, but also showed decreased phagocytic 29 gene expression and increased epithelial-associated gene expression, characteristic of 30 metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that 31 juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, Csf1r 32 deficiency disrupts embryonic to adult macrophage development. Csf1r-deficient zebrafish 33 are viable and permit analyzing the consequences of macrophage loss throughout life. 34 35 36 106 fate mapping and gene expression profiling, we identified csf1r DM mpeg1+ cells as 107 metaphocytes, a population of ectoderm-derived macrophage-like cells recently reported in 108 zebrafish (Alemany et al., 2018a; Lin et al., 2019). Extending our analyses, we further 109 demonstrated that adult csf1r DM fish exhibit a global defect in macrophage generation. In 110 5 conclusion, our study highlights distinct requirements for Csf1r during macrophage 111 generation and metaphocyte ontogeny, resolving part of the presumed macrophage 112 heterogeneity and their sensitivity to loss of Csf1r. 113 Results 114Zebrafish embryonic macrophages are formed independently of csf1r but display 115 migration and proliferation defects 207 both csf1r DM primitive macrophages and early microglia. 208Next, we assessed the presence of macrophages in developing csf1r DM animals by in 209 vivo fluorescence imaging of one lateral side of entire, individual larvae on 4 consecutive 210 days, starting at 5 dpf. We visualized ~450 macrophages in control animals, whereas csf1r DM 211 animals contained > 4-fold fewer (~100) ( Figure 3D). Over the next 4 days, macrophage 212 numbers in both groups remained stable ( Figure 3D). This suggests that, at this stage, there 213 is neither proliferative expansion of embryonic macrophages nor supply of macrophages 214 from an alternative source, causing macrophage numbers in csf1r DM larvae to remain much 215 lower than those in controls up to 9 dpf. Together these data indicate that, onwards from the 216 initiation of embryonic tissue colonization, proliferative expansion of macrophages remains 217 halted in csf1r DM animals.218 219 csf1r DM skin lacks highly branched putative Langerhans cells 220 8Given that macrophages are produced by consecutive waves of primiti...

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“…The macrophage is one such immune cell that has drastically different effects on the tumor depending on its activation or polarization state [ 10 ]. Classically-activated macrophages, or M1s, drive Th1 responses and are generally polarized by stimulants such as INFγ, LPS, and other Toll-like receptor ligands.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages

Groot

Pienta

2018

Oncotarget

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The progression of cancer is a result of not only the growth of the malignant cells but also the behavior of other components of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are key components of the TME that influence tumor growth and disease progression. TAMs can either inhibit or support tumor growth depending on their polarization to classically-activated macrophages (M1s) or alternatively-activated macrophages (M2s), respectively. Epigenetic regulation plays a significant role in determining this polarization and manipulating the epigenetic regulation in macrophages would provide a means for selectively targeting M2s thereby eliminating tumor-supporting TAMs while sparing tumor-inhibiting M1 TAMs. Many pharmacologic modulators of epigenetic enzymes are currently used clinically and could be repurposed for treating tumors with high TAM infiltrate. While much research involving epigenetic enzymes and their modulators has been performed in M1s, significantly less is known about the epigenetic regulation of M2s. This review highlights the field’s current knowledge of key epigenetic enzymes and their pharmacologic modulators known to influence macrophage polarization.

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TAM macrophages promote growth and metastasis within the cancer ecosystem

Cited by 30 publications

References 11 publications

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages

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