Macrophages and the hypoxic tumour microenvironment

Knowles, Helen J.; Harris, Adrian L.

doi:10.2741/2389

Cited by 69 publications

(81 citation statements)

References 133 publications

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“…CXCR4/CXCL12 is a known pathway implicated in TAM accretion in hypoxic areas of tumor microenvironments (22). Our results are in agreement with Beider and colleagues, who described that multiple myeloma cells recruit monocytes to their microenvironmental niche, differentiate them to macrophages that then polarize into M2-like phenotype through CXCR4/CXCL12 (51).…”

Section: Discussionsupporting

confidence: 82%

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Post-Sepsis State Induces Tumor-Associated Macrophage Accumulation through CXCR4/CXCL12 and Favors Tumor Progression in Mice

Mota

Leite

Souza

et al. 2016

Cancer Immunology Research

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Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic proliferation, however, remains unclear. Tumorassociated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNFa, TGFb, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFb, CXCL12, and TNFa were increased. Na€ ve mice inoculated with B16 together with macrophages from post-sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis-induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/ CXCL12, which contributed to B16 melanoma progression.

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Section: Discussionsupporting

confidence: 82%

“…In addition, Tymoszuk and colleagues report the contribution of in situ TAM proliferation in a mouse model of spontaneous breast cancer (20). On the other hand, the CXCR4/CXCL12 axis keeps TAMs in a tumor's hypoxic areas, thus contributing to neoangiogenesis and oxygen delivery (21,22).…”

Section: Introductionmentioning

confidence: 99%

Post-Sepsis State Induces Tumor-Associated Macrophage Accumulation through CXCR4/CXCL12 and Favors Tumor Progression in Mice

Mota

Leite

Souza

et al. 2016

Cancer Immunology Research

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“…Local hypoxic environment impacts transendothelial monocyte migration and recruitment by upregulating the expression of endothelial cell adhesion molecules and of various chemoattracting factors, i.e., vascular endothelial growth factor (VEGF), endothelin (ET), endothelial monocytes-activating polypeptide II (EMAPII), angiopoietin-2 (Ang-2), CD11b and CD18 (α M -integrin and β 2 -integrin, respectively), and CXCL12, which contributes to fine tuning of monocyte migration into inflammatory and tumor sites [82][83][84][85][86]. All these conditions make M1 macrophages (tumor inhibiting) to M2 phenotype (tumor promoting) because, at this stage, there are very few hallmarks of inflammation, i.e., edema, pain, redness, and increased body temperature or fever.…”

Section: Adenosine and Macrophage Interaction In Tumor Microenvironmentmentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

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Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

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“…This association is not unexpected; in fact, TAM tend to accumulate in necrotic (low oxygen) regions in tumors. This preferential regionalization is partially regulated by tumor hypoxia that, in turn, induces the expression of HIF-1 and other molecules (i.e., VEGF, CXCL12, CXCR4) that modulate TAM migration in vascular regions (Talks et al, 2000;Knowles and Harris, 2007). Lastly, in a very recent study, it was shown that the regulation of angiogenic processes in melanoma microenvironment could be controlled in both a paracrine and autocrine manner by TAM-derived adenomedullina (ADM) .…”

Section: Tumor-associated Macrophages (Tam)mentioning

confidence: 99%