Differential expression of TIM-3 in circulation and tumor microenvironment of colorectal cancer patients

Khalaf, Sarah; Toor, Salman M; Murshed, Khaled; Kurer, Mohamed A; Ahmed, Ayman Abdelhafiz; Nada, Mohamed Abu; Elkord, Eyad

doi:10.1016/j.clim.2020.108429

Cited by 15 publications

(12 citation statements)

References 23 publications

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“…Cytometry. Fresh whole blood staining was performed using 100 μl of blood for each sample, as previouly described [15]. Briefly, FcR Blocking Reagent (Miltenyi Biotec) was added first to block Fc receptors.…”

Section: Immunophenotyping Using Multiparametric Flowmentioning

confidence: 99%

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Toor

Khalaf

Murshed

et al. 2020

Journal of Immunology Research

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Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that have been implicated in the development of an immunosuppressive environment, which promotes tumorigenesis and tumor progression. Numerous studies have reported expansion of MDSCs in circulation and the tumor microenvironment (TME) of cancer patients. However, due to the heterogenic nature of MDSCs and the different approaches for their identification, their detailed characterization and impact on disease progression in cancer patients are warranted. In this study, we investigated the levels of different myeloid cell subsets and antigen-presenting cells (APCs) using flow cytometry in unfractionated whole blood (WB), peripheral blood mononuclear cells (PBMCs), tumor tissue (TT), and adjacent normal tissue (NT) of colorectal cancer (CRC) patients. We found high levels of granulocytic myeloid cells (GMCs) in whole blood, but their levels were significantly lower in PBMCs. Importantly, we found significantly higher levels of GMCs in the TME compared to NT. In addition, monocytic myeloid cells (MMCs) showed significantly higher levels in PBMCs of CRC patients, compared to healthy donors (HDs). Notably, patients with advanced disease stages showed significantly higher levels of GMCs compared to early stages in whole blood, but PBMCs and tumor-infiltrating myeloid cells did not show any significant differences. Lastly, we found that levels of GMCs decreased, while IMCs increased in the TME with tumor budding. Our results highlight the importance of investigating the levels of different myeloid cell subsets in PBMCs versus whole blood of cancer patients and improve current knowledge on the potential prognostic significance of myeloid cells in CRC patients.

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Section: Immunophenotyping Using Multiparametric Flowmentioning

confidence: 99%

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Toor

Khalaf

Murshed

et al. 2020

Journal of Immunology Research

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“…The most widely studied ones now are PD-1, PD-L1, and CTLA-4 ( 15 ). In addition, the potential of checkpoints such as LAG-3 ( 16 ), TIM-3 ( 17 , 18 ) and TIGIT ( 19 ) in tumor immunity also requires further studying ( Table 1 ).…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapies catering to the unmet medical need of cold colorectal cancer

Yuan

Gao

et al. 2022

Front. Immunol.

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As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming “immune escape” pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system’s capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.

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“…TIM-3 is predominantly expressed on monocytic myeloid cells and APCs in circulation, but mainly expressed on T cells and APCs in the TME. 205 TIM-3 interacts with multiple ligands, including carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1), Galectin-9 (gal-9), high-mobility group box 1 (HMGB1), and phosphatidylserine. 206 Tumor cell-intrinsic TIM-3 enhances tumor growth through NF-κB phosphorylation, which in turn activates IL-6/STAT3 axis.…”

Section: Tim-3mentioning

confidence: 99%

“…Of note, TIM‐3 expression on different immune cells is largely distinct in circulation and TME of patients with cancer. TIM‐3 is predominantly expressed on monocytic myeloid cells and APCs in circulation, but mainly expressed on T cells and APCs in the TME 205 . TIM‐3 interacts with multiple ligands, including carcinoembryonic antigen‐related cell adhesion molecule 1(CEACAM1), Galectin‐9 (gal‐9), high‐mobility group box 1 (HMGB1), and phosphatidylserine 206 …”

Section: Development Of T‐cell Exhaustionmentioning

confidence: 99%

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Hossain

Liu

Dai

et al. 2020

Medicinal Research Reviews

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Immunotherapy has revolutionized the treatment of cancer in recent years and achieved overall success and long‐term clinical benefit in patients with a wide variety of cancer types. However, there is still a large proportion of patients exhibiting limited or no responses to immunotherapeutic strategy, some of which were even observed with hyperprogressive disease. One major obstacle restricting the efficacy is that tumor‐reactive CD8+ T cells, which are central for tumor control, undergo exhaustion, and lose their ability to eliminate cancer cells after infiltrating into the strongly immunosuppressive tumor microenvironment. Thus, as a potential therapeutic rationale in the development of cancer immunotherapy, targeting or reinvigorating exhausted CD8+ T cells has been attracting much interest. Hitherto, both intrinsic and extrinsic mechanisms that govern CD8+ T‐cell exhaustion have been explored. Specifically, the transcriptional and epigenetic landscapes have been depicted utilizing single‐cell RNA sequencing or mass cytometry (CyTOF). In addition, cellular metabolism dictating the tumor‐infiltrating CD8+ T‐cell fate is currently under investigation. A series of clinical trials are being carried out to further establish the current strategies targeting CD8+ T‐cell exhaustion. Taken together, despite the proven benefit of immunotherapy in cancer patients, additional efforts are still needed to fully circumvent limitations of exhausted T cells in the treatment. In this review, we will focus on the current cellular and molecular understanding of metabolic changes, epigenetic remodeling, and transcriptional regulation in CD8+ T‐cell exhaustion and describe hypothetical treatment approaches based on immunotherapy aiming at reinvigorating exhausted CD8+ T cells.

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Differential expression of TIM-3 in circulation and tumor microenvironment of colorectal cancer patients

Cited by 15 publications

References 23 publications

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Immunotherapies catering to the unmet medical need of cold colorectal cancer

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

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Differential expression of TIM-3 in circulation and tumor microenvironment of colorectal cancer patients

Cited by 15 publications

References 23 publications

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Immunotherapies catering to the unmet medical need of cold colorectal cancer

Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

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Product

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Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy