Transcriptome of CD8+ tumor-infiltrating T cells: a link between diabetes and colorectal cancer

Saleh, Reem; Nair, Varun Sasidharan; Murshed, Khaled; Nada, Mohamed Abu; Elkord, Eyad; Shaheen, Ranad

doi:10.1007/s00262-021-02879-7

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…In TME, some effector molecules, including interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α), secreted by tumor-infiltrating CD8 + T cells, are decreased, while some molecular markers on cancer cells, such as T cell immunoglobulin and mucin domain-containing 3 (TIM-3) and programmed death 1 (PD-1) are increased, indicating that infiltrating CD8 + T cells are in a state of exhaustion and cannot play a normal anti-tumor effect [97]. Studies have shown that the increased expression of genes related to FAs metabolism, oxidative stress and ATP production in CRC CD8 + TIL of diabetes patients may inhibit the function of CD8 + T cells [98].…”

Section: Metabolic Changes In T Cellsmentioning

confidence: 99%

The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment

Zhong¹,

GUO²,

ZHANG³

et al. 2022

Oncology Research

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Lipid is a key component of plasma membrane, which plays an important role in the regulation of various cell biological behaviors, including cell proliferation, growth, differentiation and intracellular signal transduction. Studies have shown that abnormal lipid metabolism is involved in many malignant processes, including colorectal cancer (CRC). Lipid metabolism in CRC cells can be regulated not only by intracellular signals, but also by various components in the tumor microenvironment, including various cells, cytokines, DNA, RNA, and nutrients including lipids. In contrast, abnormal lipid metabolism provides energy and nutrition support for abnormal malignant growth and distal metastasis of CRC cells. In this review, we highlight the remodeling roles of lipid metabolism crosstalk between the CRC cells and the components of tumor microenvironment.

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Section: Metabolic Changes In T Cellsmentioning

confidence: 99%

The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment

Zhong¹,

GUO²,

ZHANG³

et al. 2022

Oncology Research

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show abstract

“… 6 On the other hand, tumor-infiltrating T cells, a vital component of adaptive immunity, have been shown to mediate the development of colon cancer. 1 , 7 , 8 Therefore, it is feasible to explore the interaction between colon cancer cells and immune response, which could contribute to the development of more effective treatment options for inflammation-associated cancers.…”

mentioning

confidence: 99%

Blockade of IDO-Kynurenine-AhR Axis Ameliorated Colitis-Associated Colon Cancer via Inhibiting Immune Tolerance

Zhang

Liu

Zhou

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Proinflammatory cytokines produced in tumor microenvironment resulted in eradication of anti-tumor immunity and enhanced tumor cell survival. Kynurenine (Kyn) was required for IDO-mediated T cells function via aryl hydrocarbon receptor (AhR)/Foxp3. Additionally, T cell-mediated adaptive immunity indeed played a critical role in CRC progression. Inhibition of IDO could be an effective strategy for the prevention and treatment of inflammation-related CRC.BACKGROUND & AIMS: Chronic inflammation in colon section is associated with an increased risk of colorectal cancer (CRC). Proinflammatory cytokines were produced in a tumor microenvironment and correlated with poor clinical outcome. Tumor-infiltrating T cells were reported to be greatly involved in the development of colon cancer. In this study, we demonstrated that kynurenine (Kyn), a metabolite catalyzed by indoleamine 2,3-dioxygenase (IDO), was required for IDOmediated T cell function, and adaptive immunity indeed played a critical role in CRC.METHODS: Supernatant of colon cancer cells was used to culture activated T cells and mice spleen lymphocytes, and the IDO1-Kyn-aryl hydrocarbon (AhR) receptor axis was determined in vitro. In vivo, an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC model was established in IDO -/-, Rag1 -/-, and wild-type mice, and tumor-associated T lymphocyte infiltration and Kyn/AhR signaling pathway changes were measured in each group. RESULTS: Kyn promoted AhR nuclear translocation increased the transcription of Foxp3, a marker of regulatory T cells (Tregs), through improving the interaction between AhR and Foxp3 promoter. Additionally, compared WT mice, IDO -/mice treated with AOM/DSS exhibited fewer and smaller tumor burdens in the colon, with less Treg and more CD8 þ T cells infiltration, while Kyn administration abolished this regulation. Rag1 -/mice were more sensitive to AOM/DSS-induced colitisassociated colon cancer (CRC) compared with the wild-type mice, suggesting that T cell-mediated adaptive immunity indeed played a critical role in CRC. CONCLUSIONS:We demonstrated that inhibition of IDO diminished Kyn/AhR-mediated Treg differentiation and could be an effective strategy for the prevention and

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Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer

Jiang

Thapa

Hao

et al. 2022

Antioxidants & Redox Signaling

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Transcriptome of CD8+ tumor-infiltrating T cells: a link between diabetes and colorectal cancer

Cited by 4 publications

References 45 publications

The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment

The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment

Blockade of IDO-Kynurenine-AhR Axis Ameliorated Colitis-Associated Colon Cancer via Inhibiting Immune Tolerance

Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer

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