Immune Effects of γδ T Cells in Colorectal Cancer: A Review

Ma, Ruiqiong; Yuan, Dawei; Guo, Yanxia; Yan, Rong; Li, Kang

doi:10.3389/fimmu.2020.01600

Cited by 47 publications

(35 citation statements)

References 95 publications

(165 reference statements)

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“… 29 Gamma delta T cells can effectively recognize and kill CRC cells, thereby suppressing tumor progression via multiple mechanisms. 30 The densities of tumor-infiltrating T cells in CRC tissues were higher than those in normal tissues, with higher densities indicating a good prognosis. 30–32 Subtype A and low PRG_score, with a better prognosis, showed higher infiltration of activated memory CD4+ and CD8 + T cells and gamma delta T cells, suggesting that they play a positive role in CRC development.…”

Section: Discussionmentioning

confidence: 88%

“… 30 The densities of tumor-infiltrating T cells in CRC tissues were higher than those in normal tissues, with higher densities indicating a good prognosis. 30–32 Subtype A and low PRG_score, with a better prognosis, showed higher infiltration of activated memory CD4+ and CD8 + T cells and gamma delta T cells, suggesting that they play a positive role in CRC development. The infiltration of Tregs, which suppress the anti-cancer immune response, was associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 88%

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Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer

et al. 2021

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Pyroptosis is a newly discovered programmed cell death that is associated with tumor progression, prognosis, and treatment response. However, the potential roles of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remain unclear. We described the alterations of PRGs in 1109 colorectal cancer (CRC) samples from genetic and transcriptional fields and evaluated their expression patterns from four independent datasets. We identified two distinct molecular subtypes and found that multi-layer PRG alterations were correlated with patient clinicopathological features, prognosis, and TME cell-infiltrating characteristics. Then, a PRG_score for predicting recurrence-free survival (RFS) was constructed and its predictive capability in CRC patients was validated. Consequently, we constructed a highly accurate nomogram for improving the clinical applicability of the PRG_score. A low PRG_score, characterized by increased microsatellite instability-high (MSI-H), mutation burden, and immunity activation, indicated favorable odds of RFS. Moreover, the PRG_score was significantly associated with the cancer stem cell (CSC) index and chemotherapeutic drug sensitivity. Our comprehensive analysis of PRGs in CRC demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. These findings may improve our understanding of PRGs in CRC and pave a new path for the assessment of prognosis and the development of more effective immunotherapy strategies.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 88%

Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer

et al. 2021

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“…The natural killer cells were also high in HAcluster_B. However, activated CD8 T cells, the most powerful effectors in the anticancer immune system ( 56 ), along with other important tumor killer cells and gamma delta T cells ( 57 ) were both lower in HAcluster B than that in HAcluster_A and HAcluster_C. It is known that myeloid-derived suppressor cells (MDSC) ( 58 ) and regulatory T cells are immune suppressive cells ( 59 ), while type 2 T helper cells are pro-tumorigenic ( 60 ).…”

Section: Resultsmentioning

confidence: 99%

Histone Acetylation Regulator-Mediated Acetylation Patterns Define Tumor Malignant Pathways and Tumor Microenvironment in Hepatocellular Carcinoma

Liao

Luo

et al. 2022

Front. Immunol.

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BackgroundHistone acetylation modification is one of the most common epigenetic methods used to regulate chromatin structure, DNA repair, and gene expression. Existing research has focused on the importance of histone acetylation in regulating tumorigenicity, tumor progression, and tumor microenvironment (TME) but has not explored the potential roles and interactions of histone acetylation regulators in TME cell infiltration, drug sensitivity, and immunotherapy.MethodsThe mRNA expression and genetic alterations of 36 histone acetylation regulators were analyzed in 1599 hepatocellular carcinoma (HCC) samples. The unsupervised clustering method was used to identify the histone acetylation patterns. Then, based on their differentially expressed genes (DEGs), an HAscore model was constructed to quantify the histone acetylation patterns and related subtypes of individual samples. Lastly, the relationship between HAscore and transcription background, tumor clinical features, characteristics of TME, drug response, and efficacy of immunotherapy were analyzed.ResultsWe identified three histone acetylation patterns characterized by high, medium, and low HAscore. Patients with HCC in the high HAscore group experienced worse overall survival time, and the cancer-related malignant pathways were more active in the high HAscore group, comparing to the low HAscore group. The high HAscore group was characterized by an immunosuppressive subtype because of the high infiltration of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells. Following validation, the HAscore was highly correlated with the sensitivity of anti-tumor drugs; 116 therapeutic agents were found to be associated with it. The HAscore was also correlated with the therapeutic efficacy of the PD-L1 and PD-1 blockade, and the response ratio was significantly higher in the low HAscore group.ConclusionTo the best of our knowledge, our study is the first to provide a comprehensive analysis of 36 histone acetylation regulators in HCC. We found close correlations between histone acetylation patterns and tumor malignant pathways and TME. We also analyzed the therapeutic value of the HAscore in targeted therapy and immunotherapy. This work highlights the interactions and potential clinical utility of histone acetylation regulators in treatment of HCC and improving patient outcomes.

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“…Since Trm represent a large fraction of the immune system and maintain barrier immunity against the intestinal microbiota, the loss of such cells is likely to contribute to the inflammatory events that precede carcinogenesis. Furthermore, patients with FAP showed a marked deficiency in γδ T cells in epithelial tissue - cells with a unique ability to kill tumor cells 24, 25 . Increased IgA, but not IgG responses to epithelial microbes were observed, suggesting increased bacterial translocation into colonic tissue driving mucosal antibody secretion.…”

Section: Discussionmentioning

confidence: 99%

Dysbiosis in pre-cancerous mucosa may drive immune dysfunction – a study of immune system: microbiota interaction in familial adenomatous polyposis

Noble

Durant

et al. 2021

Preprint

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Objectives: Familial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli (APC) gene that results in intestinal adenoma formation and colorectal cancer (CRC), necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis. Methods: Colonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens. Intraepithelial and lamina propria lymphocytes were phenotyped. Intraepithelial microbes were labelled with anti-IgA/IgG and analyzed by flow cytometry. Results: Proportions of resident memory CD103-expressing CD8+ and γδ T cell receptor+ intraepithelial lymphocytes were dramatically reduced in both left and right colon of patients with FAP compared to healthy controls. In lamina propria, T-cells expressed less CD103 and CD4+ CD103+ cells expressed less CD73 ectonucleotidase. IgA coating of epithelia-associated bacteria, IgA+ peripheral B cells and CD4 T-cell memory responses to commensal bacteria were increased in FAP. Conclusions: Loss of resident memory T-cells and γδ T-cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this pre-cancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC.

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Immune Effects of γδ T Cells in Colorectal Cancer: A Review

Cited by 47 publications

References 95 publications

Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer

Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer

Histone Acetylation Regulator-Mediated Acetylation Patterns Define Tumor Malignant Pathways and Tumor Microenvironment in Hepatocellular Carcinoma

Dysbiosis in pre-cancerous mucosa may drive immune dysfunction – a study of immune system: microbiota interaction in familial adenomatous polyposis

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