Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response

Wang, Keke; He, Kai-Yue; Yang, Jingyu; Liu, Mengjie; Guo, Jin-Rong; Liang, Jiyong; Wang, Jinhua; Xu, Zhixiang; Jian, Yong‐Ping

doi:10.3389/fcell.2022.842153

Cited by 10 publications

(4 citation statements)

References 53 publications

(64 reference statements)

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“…This observation raises the question whether the oral microbiome influenced the higher T cell frequency at this site, since it is reported that microbes residing in the oral cavity could affect the TIME by enhancing the influx of T cells. 32 However, when comparing the immune composition of tumor-adjacent mucosal tissue originating from oral cavity to mucosa from the larynx and hypopharynx, a difference was not detected. This suggests that the oral microbiome, at least in normal tissue, did not affect the abundance of T cells at this anatomical site.…”

Section: Discussionmentioning

confidence: 95%

Comparative analysis of immune infiltrates in head and neck cancers across anatomical sites

Muijlwijk,

Nijenhuis,

Ganzevles

et al. 2024

J Immunother Cancer

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BackgroundThe response rate to immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) receptor is 13%–18% for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Detailed understanding of the tumor immune microenvironment (TIME) is crucial in order to explain and improve this response rate. HNSCCs arise at various anatomical locations including the oral cavity, hypopharynx, larynx and oropharynx. Studies directly comparing immune infiltration between anatomical sites are scarce. Since the distinct locations could drive deviating microenvironments, we questioned whether the immune composition varies across these HNSCC sites.MethodsHere, we characterized the TIME of 76 fresh tumor specimens using flow cytometry and performed single-cell RNA-sequencing on nine head and neck tumor samples.ResultsWe found major differences in the composition of the TIME between patients. When comparing anatomical sites: tumors originating from the oral cavity had higher T cell infiltrates than tumors from other anatomical sites. The percentage of tumor-infiltrating T-lymphocytes positive for the immune checkpoint PD-1 varied considerably between patients, with the highest fraction of PD-1+ T cells found in larynx squamous cell carcinomas (SCCs). While we had hypothesized that the anatomical sites of tumor origin would drive sample clustering, our data showed that the type of TIME was more dominant and was particularly driven by the fraction of T cells positive for PD-1. Moreover, a high proportion of PD-1+ CD8+ T cells associated with an improved overall survival. Using single-cell RNA-sequencing, we observed that PD-1 expression was highest in the CD8-ENTPD1 tissue resident memory T cell/exhausted T cell and CD4-CXCL13 type 1 T helper cell clusters.ConclusionsWe found that oral cavity SCCs had the highest frequencies of T cells. We also observed considerable interpatient heterogeneity for PD-1 on T cells, with noticeably higher frequencies of PD-1+ CD4+ T helper cells in larynx SCCs. Within the entire cohort, a higher fraction of CD8+ T cells positive for PD-1 was linked to improved overall survival. Whether the fraction of PD-1+ T cells within the TIME enables immune checkpoint inhibitor response prediction for patients with head and neck cancer remains to be determined.

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Section: Discussionmentioning

confidence: 95%

Comparative analysis of immune infiltrates in head and neck cancers across anatomical sites

Muijlwijk,

Nijenhuis,

Ganzevles

et al. 2024

J Immunother Cancer

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“…Endogenous peroxidase blocking, antibody action, and development were performed as reported 51 . Quantification of positive areas in intestinal epithelial cells was completed using IHC plugin of ImageJ software 52 , 53 .…”

Section: Methodsmentioning

confidence: 99%

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid

He,

Lei,

et al. 2023

Gut Microbes

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Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila ( A. muciniphila ) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila . Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

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“…The slides were then incubated with biotinylated secondary antibodies and developed using peroxidase streptavidin and 3,3'-diaminobiphenylamine tetrahydrochloride (DAB) for 1 min. The nuclei were finally stained with hematoxylin [36] .…”

Section: Immunohistochemistrymentioning

confidence: 99%

3-Epi-betulinic acid 3- O- β- D-glucopyranoside (eBAG) induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

Liu¹,

Liu²,

He³

et al. 2024

Food Science and Human Wellness

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Epi-betulinic acid 3-O-β-D-glucopyranoside (eBAG) is a pentacyclic triterpene mainly distributed in food and medicinal plants, which exhibits various pharmacological properties. However, whether these functions are attributed to eBAG or additional components in these plants remain unknown. Herein, we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells. EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells. The eBAG-induced cell death was inhibited by knock-down of autophagy related gene (ATG) 5 and ATG7, by administration of 3-methyladenine, a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase (PI3K), and by chloroquine, a classic autophagy fl ux inhibitor. We demonstrated that eBAG induced an autophagy-mediated cell death. Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP, activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR. Co-treatment with compound C, an AMPK inhibitor, abrogated cell death induced by eBAG. We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice. As a functional food ingredient, eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.

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Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response

Cited by 10 publications

References 53 publications

Comparative analysis of immune infiltrates in head and neck cancers across anatomical sites

Comparative analysis of immune infiltrates in head and neck cancers across anatomical sites

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid

3-Epi-betulinic acid 3- O- β- D-glucopyranoside (eBAG) induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

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