CEACAM1 regulates CD8<sup>+</sup>T cell immunity and protects from severe pathology during<i>Citrobacter rodentium</i>induced colitis

Zöller, Julia; Ebel, Jana-Fabienne; Khairnar, Vishal; Schmitt, Verena; Klopfleisch, Robert; Meiners, Jana; Seiffart, Virginia; Hansen, Wiebke; Buer, Jan; Singer, Bernhard B.; Lang, Karl S.

doi:10.1080/19490976.2020.1775464

Cited by 9 publications

(14 citation statements)

References 64 publications

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“…Moreover, accumulating studies suggest that CEACAM1 is gradually along tumor development and progression. Recent studies have shown that CEACAM1 regulates CD8 + T cell immunity and induces T cell exhaustion (Zöller et al, 2020). Consistent with the above results, our data showed that the expression of CEACAM1 was higher in more advanced stages, especially in stage Ⅲ/Ⅳ respect to stage Ⅱ, indicating its promotional role in HNSCC metastasis.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, substitutive tests in normal epithelium and benign epithelial tumors are required to confirm the importance of TIM-3 and CEACAM1 in tumorigenesis of HNSCC. Furthermore, new findings indicated the expression of TIM-3 and its ligand CEACAM1 on both CD4 + and CD8 + TILs could protect T cells from apoptosis, promote the expansion of the immunosuppressive cell population, but also induce T cell exhaustion (Zöller et al, 2020;Dixon et al, 2021;Yang et al, 2021), suggesting that anti-TIM-3/CEACAM1 axis therapy is promising candidate for combination with other therapeutic modalities diminish regulatory T cells or costimulate CD8 T cells to treat head and neck carcinoma. We need further work to explore the specific mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…These associations are responsible for a multitude of processes that converge into complex and interwoven roles in tumorigenesis and metastatic development. New findings indicated CEACAM1 was an important regulator of CD8 + T cell function (Zöller et al, 2020). CEACAM1 was described to be downregulated or overexpressed in numerous tumors, and it has been considered as a promising candidate biomarker for some cancers.…”

Section: Introductionmentioning

confidence: 99%

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TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Yang

Zeng

et al. 2021

Front. Mol. Biosci.

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Background: T-cell Immunoglobulin and Mucin domain-containing molecule-3 (TIM-3) is a new immune checkpoint molecule which plays important and complex roles in regulating immune responses and in inducing immune tolerance. TIM-3 is expressed on activated T cells and its signaling on cytotoxic T cells leads to T cell exhaustion which is mediated by carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on tumor tissues and/or tumor infiltrating lymphocytes (TILs).Methods: In the present study, we investigated TIM-3 and CEACAM1 immunohistochemical expression in 80 head and neck squamous cell carcinoma (HNSCC) specimens, linked to detailed outcome, clinic-pathological parameters. Here we reported scores and absolute counts of TIM-3+/CEACAM1+ TILs, and evaluated the expression of CEACAM1 on tumor tissues.Results: The results showed that more TIM-3+ TILs infiltration correlated with poorer overall survival (p < 0.001), as did the presence of CEACAM1 on cancer cells (p < 0.001) and CEACAM1+ TILs in tumor microenvironment (p = 0.015). Multivariate Cox regression analysis revealed that high TIM-3+ TILs may be considered as an independent prognostic factor of poor disease outcome (hazard ratio, 2.066; 95% confidence interval, 1.027–4.159; p = 0.042), as well as cancer cells expressed CEACAM1 level (hazard ratio, 5.885; 95% confidence interval, 2.832–12.230; p < 0.001).Conclusion: Our results indicate that expression of TIM-3 and CEACAM1 may represent a highly dysfunctional population of T cells. Our current findings suggest both of them were valuable predicting markers that might provide help for clinicians to design effective immunotherapeutic regimen against head and neck carcinoma.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Yang

Zeng

et al. 2021

Front. Mol. Biosci.

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“…In addition to creating a pro-inflammatory environment that promotes oncogenesis and development of CRC, F. nucleatum can also remodel the tumor microenvironment to evade the anticancer immune response. Fap2, an outer surface protein of F. nucleatum , binds to and activates the inhibitory receptors, T cell Ig, ITIM Domain receptor (TIGIT) 42 , and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) 107 expressed by T cells and NK cells, which protect F. nucleatum and tumor cells from being killed by immune cells. TIGIT is highly expressed in lymphocytes of CRC tissues 108 , while CEACAM1, which is an inhibitory receptor for various immune cell subsets, is expressed on the surface of numerous types of tumor cells and is considered to be a specific biomarker associated with tumor progression, metastasis, and poor prognosis 108 .…”

Section: Carcinogenic Mechanism Of Specific Intestinal Bacteriamentioning

confidence: 99%

Tumorigenic bacteria in colorectal cancer: mechanisms and treatments

Li¹,

Liu²,

Zheng³

et al. 2021

Cancer Biol. Med.

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Colorectal cancer (CRC) is the third most common and the second most fatal cancer. In recent years, more attention has been directed toward the role of gut microbiota in the initiation and development of CRC. Some bacterial species, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, Enterococcus faecalis, and Salmonella sp. have been associated with CRC, based upon sequencing studies in CRC patients and functional studies in cell culture and animal models. These bacteria can cause host DNA damage by genotoxic substances, including colibactin secreted by pks + Escherichia coli, B. fragilis toxin (BFT) produced by Bacteroides fragilis, and typhoid toxin (TT) from Salmonella. These bacteria can also indirectly promote CRC by influencing host-signaling pathways, such as E-cadherin/β-catenin, TLR4/MYD88/NF-κB, and SMO/RAS/p38 MAPK. Moreover, some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function, creating a proinflammatory environment, or influencing the autophagy process. Treatments with the classical antibacterial drugs, metronidazole or erythromycin, the antibacterial active ingredients, M13@ Ag (electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13), berberine, and zerumbone, were found to inhibit tumorigenic bacteria to different degrees. In this review, we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria, as well as progress in developing effective antibacterial therapies. Specific bacteria have been shown to be active in the oncogenesis and progression of CRC, and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC. These bacteria may be useful as biomarkers or therapeutic targets for CRC.

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“…Recent studies suggest that CEACAM1 expression in T cells results in inhibition of activated T cells, and it may regulate cells that provide inhibitory signals 15 . However, newer reports clearly show that CEACAM1 expression in B and T cells is crucial for regulation of the resolution of viral and bacterial infections 16‐18 . Thus, the potential role of CEACAM1 as a clinically highly relevant diagnostic and therapeutic target for various malignant diseases has nowadays gained increasing attention.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of carcinoembryonic antigen‐related cell adhesion molecule 1 blood serum levels in women at high risk for preeclampsia

Mach

Andrikos

Schmidt

et al. 2020

American J Rep Immunol

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Problem The aim of this study was to evaluate the sCEACAM1 concentrations in serum from patients in the first trimester who have a high risk for developing PE during pregnancy. Method of the study Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) levels were determined with ELISA. The patients (n = 109) were divided into two groups: patients who have a high risk of developing PE early‐onset and a control group. Patients who have a high risk of developing PE were then divided into two subgroups depending on PE development in third trimester of pregnancy: PE in third trimester versus no PE in third trimester. Results sCEACAM1 concentrations in patients who were screened as having a high risk for developing PE were significantly higher than in healthy pregnant women in the first trimester (p = .03). The highest sCEACAM1 concentration was found in the high‐risk group with PE development compared to the control group (p = .004). Conclusion Elevated sCEACAM1 blood serum levels in women with PE suggest that there is immune dysregulation in early pregnancy, which may be helpful in PE prediction and therapy.

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CEACAM1 regulates CD8⁺T cell immunity and protects from severe pathology duringCitrobacter rodentiuminduced colitis

Cited by 9 publications

References 64 publications

TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Tumorigenic bacteria in colorectal cancer: mechanisms and treatments

Evaluation of carcinoembryonic antigen‐related cell adhesion molecule 1 blood serum levels in women at high risk for preeclampsia

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CEACAM1 regulates CD8+T cell immunity and protects from severe pathology duringCitrobacter rodentiuminduced colitis

Cited by 9 publications

References 64 publications

TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Tumorigenic bacteria in colorectal cancer: mechanisms and treatments

Evaluation of carcinoembryonic antigen‐related cell adhesion molecule 1 blood serum levels in women at high risk for preeclampsia

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CEACAM1 regulates CD8⁺T cell immunity and protects from severe pathology duringCitrobacter rodentiuminduced colitis