Antitumor Activity of Extract From the Sporoderm-Breaking Spore of Ganoderma lucidum: Restoration on Exhausted Cytotoxic T Cell With Gut Microbiota Remodeling

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC.

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Cytotoxic T-Cell Trafficking Chemokine Profiles Correlate With Defined Mucosal Microbial Communities in Colorectal Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.715559 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiali Zhang ◽

Ji Tao ◽

Ruo-Nan Gao ◽

Zhi-Yuan Wei ◽

Yu-Shan He ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cell ◽

Gut Microbiota ◽

Oral Bacteria ◽

Cytotoxic T Cell ◽

Cell Trafficking ◽

Gut Microbes ◽

T Cell Trafficking ◽

Normal Tissues ◽

Tumor Tissues

The involvement of gut microbiota in T-cell trafficking into tumor tissue of colorectal cancer (CRC) remains to be further elucidated. The current study aimed to evaluate the expression of major cytotoxic T-cell trafficking chemokines (CTTCs) and chemokine-associated microbiota profiles in both tumor and adjacent normal tissues during CRC progression. We analyzed the expression of chemokine C-X-C motif ligands 9, 10, and 11 (CXCL9, CXCL10, and CXCL11), and C-C motif ligand 5 (CCL5), characterized gut mucosa-associated microbiota (MAM), and investigated their correlations in CRC patients. Our results showed that the expression of CXCL9, CXCL10, and CXCL11 was significantly higher in tumor than in adjacent normal tissues in 136 CRC patients. Notably, the high expression of CXCL9 in tumor tissues was associated with enhanced CD8+ T-cell infiltration and improved survival. Moreover, the MAM in tumor tissues showed reduction of microbial diversity and increase of oral bacteria. Microbial network analysis identified differences in microbial composition and structure between tumor and adjacent normal tissues. In addition, stronger associations between oral bacteria and other gut microbes were observed. Furthermore, the correlation analysis between the defined MAM and individual CTTCs showed that the CTTCs’ correlated operational taxonomic units (OTUs) in tumor and adjacent normal tissues rarely overlap with each other. Notably, all the enriched OTUs were positively correlated with the CTTCs in either tumor or adjacent normal tissues. Our findings demonstrated stronger interactions between oral bacteria and gut microbes, and a shifted correlation pattern between MAM and major CTTCs in tumor tissues, underlining possible mechanisms of gut microbiota–host interaction in CRC.

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