Targeting Mononuclear Phagocyte Receptors in Cancer Immunotherapy: New Perspectives of the Triggering Receptor Expressed on Myeloid Cells (TREM-1)

Raggi, Federica; Bosco, Maria Carla

doi:10.3390/cancers12051337

Cited by 21 publications

(16 citation statements)

References 247 publications

(486 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also evaluated the macrophage cells (CD11b + F4/80 + ) in the tumors from each of the three mouse cancer models. M1 macrophages suppress tumor growth by phagocytosis and by secreting inhibitory factors (52), whereas M2 macrophages promote tumor progression (53). In all three models, we found that the combination treatment expanded the inflammatory M1 macrophage population (CD11b + F4/80 + MHC-II + CD206 − ) (Fig.…”

Section: Combination Therapy With D18 and Anti-pd-1 Antibody Increase...mentioning

confidence: 57%

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

et al. 2020

View full text Add to dashboard Cite

Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene PTEN (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103+ tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8+ T cells to tumors. In patients with melanoma, a high KDM5A gene signature correlated with KDM5A expression and could potentially serve as a marker of response to anti–PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.

show abstract

Section: Combination Therapy With D18 and Anti-pd-1 Antibody Increase...mentioning

confidence: 57%

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Among them, inflammation is now recognized as a defining hallmark of cancer (2). Indeed, strong evidence indicate that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells (3,4). Moreover, necrotic cell death from tumors generates proinflammatory signals (ie: IL-1a) in the proximal tissue microenvironment, in opposition to apoptosis and autophagy (2).…”

Section: Introductionmentioning

confidence: 99%

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

et al. 2022

View full text Add to dashboard Cite

Inflammation is recognized as one of the hallmarks of cancer. Indeed, strong evidence indicates that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells. Mononuclear phagocytes (MPs) have been identified as key contributors of the inflammatory infiltrate in several solid human neoplasia, promoting angiogenesis and cancer progression. One of the most described amplifiers of MPs pro-inflammatory innate immune response is the triggering receptors expressed on myeloid cells 1 (TREM-1). Growing evidence suggests TREM-1 involvement in oncogenesis through cancer related inflammation and the surrounding tumor microenvironment. In human oncology, high levels of TREM-1 and/or its soluble form have been associated with poorer survival data in several solid malignancies, especially in hepatocellular carcinoma and lung cancer. TREM-1 should be considered as a potential biomarker in human oncology and could be used as a new therapeutic target of interest in human oncology (TREM-1 inhibitors, TREM-1 agonists). More clinical studies are urgently needed to confirm TREM-1 (and TREM family) roles in the prognosis and the treatment of human solid cancers.

show abstract

“…TREM1 is also involved in the innate immune response associated with various infectious and noninfectious in ammation responses and autoimmune disorders (13,14). Recent studies have shown a close link between TREM1 and cancer, as TREM1 is selectively expressed on tumor-associated macrophages (TAMs) in non-small cell lung cancer (15), activates in the liver Kupffer cells and promotes the progression of hepatocellular carcinoma (16).…”

Section: Introductionmentioning

confidence: 99%

TREM1 as a Potential Prognostic Biomarker Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma

Pu¹,

Cai

Jin

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: This study aims to find immune-related hub gene as potential novel biomarker for KIRC. Methods: We constructed a KIRC immune prognostic signature. The receiver operating characteristic (ROC) curves, survival curves, univariate and multivariate Cox regression analysis were utilized to validate the signature. Immunohistochemical staining was used to detect the expression of TRME1 in renal clear cell carcinoma tissues. The clinical characteristics, the status of the tumor microenvironment, and immune infiltration were analyzed through the ESTIMATE and CIBERSORT algorithms for the hub gene, while the Gene Set Enrichment Analysis and PPI analysis were performed to predict the function of the hub gene. Results: In Immunohistochemical staining, we found that the expression of TREM1 was significantly upregulated with increasing tumor grade in renal clear cell carcinoma, and elevated TREM1 expression was associated with poor prognosis.The CIBERSORT and ESTIMATE algorithms revealed that TREM1 was correlated with the infiltration of 12 types of immune cells. Therefore, it was determined that TREM1 was involved in numerous classical pathways in the immune response via GSEA analysis. Conclusions: The results suggest that TREM1 may act as an implicit novel prognostic biomarker in KIRC that could be utilized to facilitate immunotherapeutic strategy.

show abstract

Targeting Mononuclear Phagocyte Receptors in Cancer Immunotherapy: New Perspectives of the Triggering Receptor Expressed on Myeloid Cells (TREM-1)

Cited by 21 publications

References 247 publications

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

TREM1 as a Potential Prognostic Biomarker Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma

Contact Info

Product

Resources

About