Intratumoral microbiota in HCC: A new kid on the block?

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti–PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti–PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification–dependent manner, thereby activating CD8 + T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.

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Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy

Zheng,

Chen

2024

Front. Oncol.

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Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.

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Intratumoral microbiota in HCC: A new kid on the block?

Cited by 5 publications

References 11 publications

Investigating the role of the intratumoral microbiome in thyroid cancer development and progression

Investigating the role of the intratumoral microbiome in thyroid cancer development and progression

Activation of NOD1 on tumor-associated macrophages augments CD8⁺T cell–mediated antitumor immunity in hepatocellular carcinoma

Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy

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Intratumoral microbiota in HCC: A new kid on the block?

Cited by 5 publications

References 11 publications

Investigating the role of the intratumoral microbiome in thyroid cancer development and progression

Investigating the role of the intratumoral microbiome in thyroid cancer development and progression

Activation of NOD1 on tumor-associated macrophages augments CD8+T cell–mediated antitumor immunity in hepatocellular carcinoma

Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy

Contact Info

Product

Resources

About

Activation of NOD1 on tumor-associated macrophages augments CD8⁺T cell–mediated antitumor immunity in hepatocellular carcinoma