Myeloid Cells TREM Down Anti-tumor Responses

Bugler-Lamb, Aimée R.; Guilliams, Martin

doi:10.1016/j.cell.2020.07.042

Cited by 10 publications

(8 citation statements)

References 10 publications

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“…metabolic disorders and cancer). Given the newly identified role for the TREM2/ApoE axis in cancer [132], care should be taken when evaluating those therapies that enhance TREM2, in order to prevent unwanted effects on immunosuppressive myeloid cells [133].…”

Section: A Note Of Cautionmentioning

confidence: 99%

TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation

Magno

Bunney

Mead

et al. 2021

Mol Neurodegeneration

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The central role of the resident innate immune cells of the brain (microglia) in neurodegeneration has become clear over the past few years largely through genome-wide association studies (GWAS), and has rapidly become an active area of research. However, a mechanistic understanding (gene to function) has lagged behind. That is now beginning to change, as exemplified by a number of recent exciting and important reports that provide insight into the function of two key gene products – TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) – in microglia, and their role in neurodegenerative disorders. In this review we explore and discuss these recent advances and the opportunities that they may provide for the development of new therapies.

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Section: A Note Of Cautionmentioning

confidence: 99%

TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation

Magno

Bunney

Mead

et al. 2021

Mol Neurodegeneration

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“…In recent papers 5 – 7 the role of TREM2 in cancer was elucidated showing that TREM2 is a marker of tumor-associated macrophages in cancers, that high expression of macrophage TREM2 correlates with poor survival, and that blocking TREM2 enhances anti-tumor response in mice. Thus, it is becoming clear that TREM2 is a major player at the intersection of cancer, metabolic, and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

TREM2 has a significant, gender-specific, effect on human obesity

Reich

Adato

Kofman

et al. 2023

Sci Rep

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Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) is a membrane protein expressed on immune cells, involved in neurodegenerative diseases and cancer. Recently, it was shown that TREM2 is expressed on lipid associated macrophages in adipose tissue, and that TREM2 knockout mice suffer from metabolic symptoms. Here, a computational study using public databases, brings direct evidence for the involvement of TREM2 in human obesity. First, we show a significant correlation between TREM2 expression levels and BMI in adipose tissues in samples from the GTEx database. This association was evident for males but not for females. Second, we identified in the UK Biobank cohort a coding SNP in TREM2 with a significant effect on BMI. Compared to previously identified SNPs associated with BMI, this SNP (rs2234256 SNP, L211P) has the strongest association, reflected in significantly higher BMI values of people carrying the SNP as heterozygous and even more for homozygous. Strikingly, this association was evident only for females. These observations suggest a novel gender-specific role of TREM2 in human obesity, and call for further studies to elucidate the mechanism by which this gene correlates with an obese phenotype.

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“…168,169 Within the complexity and diversity of macrophage transcriptomes described above, some commonalities seem to emerge as Determining whether these molecules play functional roles in TAMs and whether they can be exploited for therapy or diagnosis is a burning question in the field. In this context, recent evidence highlights a key role of the APOE-TREM2 axis 170 and of complement-driven inflammation 171 in immune oncology. TREM2, a key regulator of microglia during neurodegeneration 172 was validated as a marker of TAM in human cancers, the expression of which correlates with poor patient survival.…”

Section: Making S En S E Of H Uman Tam He Terog Eneit Ymentioning

confidence: 99%

Determinants, mechanisms, and functional outcomes of myeloid cell diversity in cancer

Caronni

Montaldo

Mezzanzanica

et al. 2021

Immunological Reviews

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The tumor microenvironment (TME) is a complex architecture of cells, including those of the immune system, of matrix components, and of their interactions within the unique physical traits of the cancer tissue. 1,2 Many elements influence the composition and cellular dynamics of the TME, such as the anatomical site, the type, and stage of the disease, the therapeutic regimen as well as host factors like age, sex, and comorbidities. 2 Within the extreme diversity of TMEs, parameters integrating the relative composition, spatial arrangement, and functional properties of infiltrating immune cells are useful indicators of disease progression and response to therapies. 2,3 For instance, high tumor infiltration of cytotoxic CD8 + T cells engaging inhibitory crosstalk in the TME via the programmed death (PD)1:PD-L1/PD-L2 axis often predicts efficient response to immune checkpoint blockade therapy. 3 In some cases, CD8 + T cells form organized assemblies with antigen-presenting cells such as dendritic cells (DCs), B cells, and macrophages within the tumor stroma; these so-called tertiary lymphoid structures are considered sites of efficient T-cell priming, and their presence is associated with good response to immunotherapy. 4 In this context, a subset of conventional DCs, termed cDC1, can efficiently cross-present tumor antigens for the induction of a durable immune response. 5-7 Accumulation of cDC1 at the tumor site is mediated at least in part by chemokines released by infiltrating natural killer (NK) cells, 8 a

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Myeloid Cells TREM Down Anti-tumor Responses

Cited by 10 publications

References 10 publications

TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation

TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation

TREM2 has a significant, gender-specific, effect on human obesity

Determinants, mechanisms, and functional outcomes of myeloid cell diversity in cancer

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