Anticancer efficacy of noble metal nanoparticles relies on reprogramming tumor-associated macrophages through redox pathways and pro-inflammatory cytokine cascades

Sengupta, Mahuya; Pal, Ramkrishna; Nath, Anupam; Chakraborty, Biswajit; Singh, Leichombam Mohindro; Das, Biswajit; Ghosh, Sujit Kumar

doi:10.1038/s41423-018-0046-7

Cited by 23 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their pro‐tumoral effects are exerted through promoting genetic instability, local immunosuppression, and stem cell nurturing . EGF and CD68 are specific markers for M2 cells, and CD163 is a marker related to M2 polarity . Other markers for M2 cells are listed in the Figure .…”

Section: M1 and M2 Cells: Definition And Functionmentioning

confidence: 99%

Macrophage polarity in cancer: A review

Najafi

Goradel

Farhood

et al. 2018

J of Cellular Biochemistry

401

313

View full text Add to dashboard Cite

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.

show abstract

Section: M1 and M2 Cells: Definition And Functionmentioning

confidence: 99%

Macrophage polarity in cancer: A review

Najafi

Goradel

Farhood

et al. 2018

J of Cellular Biochemistry

401

313

View full text Add to dashboard Cite

show abstract

“…Those failures are linked to impaired iNKT cell function. Although previous studies suggest that TAMs [11][12][13] , myeloid derived suppressor cells 14 , regulatory T cells 15,16 , exosomes 17 , metabolic products 18,19 , and suppressive cytokines 20 in tumors repress anti-tumor immunity and cause the failure of immunotherapies, the mechanisms underlying dysfunction of intratumoral iNKT cells still remain unclear. Elucidating the underlying mechanisms would help to design new immunotherapies augmenting the efficacy of iNKT cell-based immunotherapies.…”

mentioning

confidence: 99%

Impaired lipid biosynthesis hinders anti-tumor efficacy of intratumoral iNKT cells

Tian

et al. 2020

Nat Commun

View full text Add to dashboard Cite

Dysfunction of invariant natural killer T (iNKT) cells in tumor microenvironment hinders their anti-tumor efficacy, and the underlying mechanisms remain unclear. Here we report that iNKT cells increase lipid biosynthesis after activation, and that is promoted by PPARγ and PLZF synergically through enhancing transcription of Srebf1. Among those lipids, cholesterol is required for the optimal IFN-γ production from iNKT cells. Lactic acid in tumor microenvironment reduces expression of PPARγ in intratumoral iNKT cells and consequently diminishes their cholesterol synthesis and IFN-γ production. Importantly, PPARγ agonist pioglitazone, a thiazolidinedione drug for type 2 diabetes, successfully restores IFN-γ production in tumor-infiltrating iNKT cells from both human patients and mouse models. Combination of pioglitazone and alpha-galactosylceramide treatments significantly enhances iNKT cell-mediated anti-tumor immune responses and prolongs survival of tumor-bearing mice. Our studies provide a strategy to augment the anti-tumor efficacy of iNKT cell-based immunotherapies via promoting their lipid biosynthesis.

show abstract

“…The vital involvement of TAMs in the microenvironment of cancer has received much attention with the production of several growth factors by these accumulated cells shown to influence both human tumorigenesis and angiogenesis 40,41 . A symbiosis between cocultured macrophages and tumor cells was shown by earlier research to boost the degradation of collagen 42 .…”

Section: Discussionmentioning

confidence: 99%

BRD4 promotes tumor progression and NF-κB/CCL2-dependent tumor-associated macrophage recruitment in GIST

Sun²,

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

The most commonly occurring sarcoma of the soft tissue is gastrointestinal stromal tumor (GIST). Treatment and prevention of the disease necessitate an understanding of the molecular mechanisms involved. However, the role of BRD4 in the progression of GIST is still unclear. While it is known there are abundant infiltrating tumor-associated macrophages (TAMs) in the tumor microenvironment, the exact role of these cells has yet to be studied. This work showed an upregulation of BRD4 in GIST that was associated with GIST prognosis. Through gain and loss of function studies, it was found that BRD4 promotes GIST growth and angiogenesis in vitro and in vivo. Mechanistically, BRD4 enhances CCL2 expression by activating the NF-κB signaling pathway. Furthermore, this CCL2 upregulation causes recruitment of macrophages into the tumor leading to tumor growth. A likely mechanism for interactions in the GIST microenvironment has been outlined by this work to show the role and potential use of BRD4 as a treatment target in GIST.

show abstract

Anticancer efficacy of noble metal nanoparticles relies on reprogramming tumor-associated macrophages through redox pathways and pro-inflammatory cytokine cascades

Cited by 23 publications

References 9 publications

Macrophage polarity in cancer: A review

Macrophage polarity in cancer: A review

Impaired lipid biosynthesis hinders anti-tumor efficacy of intratumoral iNKT cells

BRD4 promotes tumor progression and NF-κB/CCL2-dependent tumor-associated macrophage recruitment in GIST

Contact Info

Product

Resources

About