The Study of Mucosal-Associated Invariant T Cells in Colon Cancer and Roles in Immune Activities

Mo, Juanfen; Li, Zheng; Gao, Zhenzhen; Wu, Jiayuan; Bao, Yi

doi:10.2147/ott.s332822

Cited by 9 publications

(14 citation statements)

References 25 publications

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“…Thus, investigating how to stimulate and strengthen the antitumour function of CD8+ Temra cells could be a new direction for CC immune therapy research. Additionally, we noticed that CD8+ MAITs were specifically infiltrated within HSIL foci, which have been reported to sense intracellular infection and modulate tissue inflammation 51–53 . Therefore, we propose that CD8+ MAIT cells play a role in immune surveillance.…”

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

“…Additionally, we noticed that CD8+ MAITs were specifically infiltrated within HSIL foci, which have been reported to sense intracellular infection and modulate tissue inflammation. [51][52][53] Therefore, we propose that CD8+ MAIT cells play a role in immune surveillance. In addition, De Biasi et al 54 previously showed that the proportions of MAIT cells were significantly higher in responders with metastatic melanoma to anti-PD1 therapy, highlighting the potential value of MAITs as biomarkers for patient responses to anti-PD-1 therapy.…”

Section: Discussionmentioning

confidence: 99%

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Spatiotemporally deciphering the mysterious mechanism of persistent HPV‐induced malignant transition and immune remodelling from HPV‐infected normal cervix, precancer to cervical cancer: Integrating single‐cell RNA‐sequencing and spatial transcriptome

Guo

Tang

et al. 2023

Clinical & Translational Med

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Background The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive. Aims Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer. Materials & Methods We generated scRNA‐seq profiles and spatial transcriptomics data from nine patient samples, including two HPV‐negative normal, two HPV‐positive normal, two HPV‐positive HSIL and three HPV‐positive cancer samples. Results We not only identified three ‘HPV‐related epithelial clusters’ that are unique to normal, high‐grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune‐suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a ‘homeostasis‐balance‐malignancy’ change occurred within the cervical microenvironment during disease progression. Discussion We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV‐related cervical oncogenesis, including normal, HPV‐positive normal, HSIL and cancer. We identified three unique HPV‐related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation. Conclusion Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Spatiotemporally deciphering the mysterious mechanism of persistent HPV‐induced malignant transition and immune remodelling from HPV‐infected normal cervix, precancer to cervical cancer: Integrating single‐cell RNA‐sequencing and spatial transcriptome

Guo

Tang

et al. 2023

Clinical & Translational Med

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“…In human CRC, studies have demonstrated both positive and negative associations between tumor-infiltrating MAIT cells and overall survival (31, 32). MAIT cells accumulate in CRC tumors (17, 31, 33) and tumor-infiltrating MAIT cells display bacterial antigen recognition signatures (34), but the impact of these cells in the tumor microenvironment is not well understood. Tumor-infiltrating MAIT cells retain their cytotoxicity and production of cytokines (17, 35), but have impaired interferon-γ (IFN-γ) production (17, 36) and high levels of exhaustion markers (33, 36).…”

Section: Introductionmentioning

confidence: 99%

“…MAIT cells accumulate in CRC tumors (17, 31, 33) and tumor-infiltrating MAIT cells display bacterial antigen recognition signatures (34), but the impact of these cells in the tumor microenvironment is not well understood. Tumor-infiltrating MAIT cells retain their cytotoxicity and production of cytokines (17, 35), but have impaired interferon-γ (IFN-γ) production (17, 36) and high levels of exhaustion markers (33, 36). A multi-omics analysis of CRC demonstrated an abundance of intratumor microbes and their immune modulation potential on tumor-infiltrating immune cells, including MAIT cells (32).…”

Section: Introductionmentioning

confidence: 99%

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Cheng,

Lebish,

Jensen

et al. 2024

Preprint

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Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1-/- mice with MC38-derived tumors and tumor growth was assessed. Peritumoral injection of MAIT cells inhibits tumor growth compared to control. Genomic and multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. Multiplex cytokine and flow cytometry analyses of human peripheral leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. We documented that MAIT cells have a protective role in a murine colon cancer model, potentially involving novel eosinophil-associated mechanisms. This study provides evidence of the immune modulating potential of MAIT cells within the tumor microenvironment, leading to compositional and functional changes. Our results highlight the potential of MAIT cells for colon cancer immunotherapy.

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Mucosal-Associated Invariant T (MAIT) Cell Differentiation and Function

Ascui,

Kronenberg

2024

Reference Module in Life Sciences

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The Study of Mucosal-Associated Invariant T Cells in Colon Cancer and Roles in Immune Activities

Cited by 9 publications

References 25 publications

Spatiotemporally deciphering the mysterious mechanism of persistent HPV‐induced malignant transition and immune remodelling from HPV‐infected normal cervix, precancer to cervical cancer: Integrating single‐cell RNA‐sequencing and spatial transcriptome

Spatiotemporally deciphering the mysterious mechanism of persistent HPV‐induced malignant transition and immune remodelling from HPV‐infected normal cervix, precancer to cervical cancer: Integrating single‐cell RNA‐sequencing and spatial transcriptome

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Mucosal-Associated Invariant T (MAIT) Cell Differentiation and Function

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