Harnessing Pyroptosis for Cancer Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 346 - 346

Published: Feb. 16, 2024

Cancer immunotherapy is a novel pillar of cancer treatment that harnesses the immune system to fight tumors and generally results in robust antitumor immunity. Although has achieved remarkable clinical success for some patients, many patients do not respond, underscoring need develop new strategies promote Pyroptosis an immunostimulatory type regulated cell death activates innate system. A hallmark pyroptosis release intracellular contents such as cytokines, alarmins, chemokines can stimulate adaptive activation. Recent studies suggest promotes Here, we review mechanisms by which be induced highlight induce cells defense. We discuss how modulates tumor microenvironment immunity also research areas focus on continued development anticancer treatment. Pyroptosis-based therapies offer promising avenue treating immunologically 'cold' tumors.

Language: Английский

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TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy

Science Immunology, Journal Year: 2024, Volume and Issue: 9(95)

Published: May 17, 2024

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering on myeloid cells 2 (TREM2) attenuates growth, lack of functional TREM2 enhances elimination anti–PD-1. Here, we found that anti–PD-1 treatment combined with deficiency in mice induces proinflammatory programs intestinal a concomitant expansion Ruminococcus gnavus microbiota. Gavage wild-type R. enhanced anti–PD-1–mediated elimination, recapitulating effect occurring absence TREM2. A environment coincided expansion, increased circulation, migration TNF-producing CD4 + T bed. Thus, remotely controls blockade through modulation microbiota, emerging as potential probiotic agent for increasing responsiveness anti-PD-1.

Language: Английский

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NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment

Science Advances, Journal Year: 2024, Volume and Issue: 10(38)

Published: Sept. 18, 2024

Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated effects hypoxia, a TME-associated feature, on functional, epigenetic, transcriptional macrophages found that hypoxia boosts immunogenicity. Hypoxic inflammatory are characterized by cluster proinflammatory genes undergoing ten-eleven translocation–mediated DNA demethylation overexpression. These regulated NF-κB, while HIF1α dominates reprogramming, demonstrated through ChIP-seq pharmacological inhibition. bladder ovarian carcinomas, hypoxic enriched in immune-infiltrated tumors, correlating better patient prognoses. Coculture assays cell-cell communication analyses support hypoxic-activated enhance T cell–mediated responses. The NF-κB–associated hypomethylation signature displayed subset macrophages, isolated from tumors. Our results challenge paradigms regarding highlight actionable target cells to modulate anticancer immune

Language: Английский

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Macrophage diversity in cancer dissemination and metastasis

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(11), P. 1201 - 1214

Published: Oct. 14, 2024

Invasion and metastasis are hallmarks of cancer. In addition to the well-recognized hematogenous lymphatic pathways metastasis, cancer cell dissemination can occur via transcoelomic perineural routes, which typical ovarian pancreatic cancer, respectively. Macrophages a universal major component tumor microenvironment and, in established tumors, promote growth secondary sites. Here, we review role tumor-associated macrophages (TAMs) emphasizing diversity myeloid cells different tissue contexts (lungs, liver, brain, bone, peritoneal cavity, nerves). The generally used models lung fail capture microenvironments. A better understanding TAM may pave way for tailored diagnostic therapeutic approaches.

Language: Английский

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Cancer cells impair monocyte-mediated T cell stimulation to evade immunity

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Abstract The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses 1,2 . Within the microenvironment, CD8 + T undergo full effector differentiation acquire cytotoxic functions in specialized niches 3–7 Although interactions with type 1 conventional dendritic have been implicated this process 3–5,8–10 , underlying cellular players molecular mechanisms remain incompletely understood. Here we show that inflammatory monocytes can adopt a pivotal role intratumoral cell stimulation. These express Cxcl9 Cxcl10 Il15 but contrast to cells, which cross-present antigens, obtain present peptide–major histocompatibility complex class I complexes from through ‘cross-dressing’. Hyperactivation of MAPK signalling hampers coordinately blunting production interferon (IFN-I) cytokines inducing secretion prostaglandin E 2 (PGE ), impairs monocyte state Enhancing IFN-I cytokine blocking PGE restores re-sensitizes tumours cell-mediated immunity. Together, our work uncovers central stimulation, elucidates how oncogenic disrupts counter-regulation IFN-I, proposes rational combination therapies enhance immunotherapies.

Language: Английский

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