CEACAM1 : modulateur central du métabolisme, de la progression tumorale,de l’angiogenèse et de l’immunité

Nouvion, Anne-Laure; Beauchemin, Nicole

doi:10.1051/medsci/2009253247

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Finally, the tumor itself responds to radiation-induced stress or damage through a panel of phenotypic changes. By releasing several cytokines, chemokines, or growth factors as well as up-regulating specific surface receptors e.g., immunosuppressive PD-L1, cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and others, tumor cells become proficient in dampening immune responses and to escape the immune system (91–96). Detailed reviews from Sharma et al as well as Wennerberg et al recently summarized the role of these tumor cell-extrinsic factors for primary and adaptive resistance so that these mechanisms will not be further addressed here (34, 41).…”

Section: Dual Face Of Radiation-induced Immune Changes: Balance Betwementioning

confidence: 99%

Targeting the Immunomodulatory CD73/Adenosine System to Improve the Therapeutic Gain of Radiotherapy

2019

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Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (CD73) that catabolize ATP to adenosine. An acute CD73-dependent increase of adenosine in normal tissues mostly exerts tissue protective functions whereas chronically increased adenosine-levels in tissues exposed to DNA damaging chemotherapy or radiotherapy promote pathologic remodeling processes and fibrosis for example in the skin and the lung. Importantly, cancer cells also express CD73 and high CD73 expression in the tumor tissue has been linked to poor overall survival and recurrence free survival in patients suffering from breast and ovarian cancer. CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cancer cells. In addition, adenosine can promote tumor intrinsic or therapy-induced immune escape by various mechanisms that dampen the immune system. Consequently, modulating CD73 or cancer-derived adenosine in the tumor microenvironment emerges as an attractive novel therapeutic strategy to limit tumor progression, improve antitumor immune responses, avoid therapy-induced immune deviation, and potentially limit normal tissue toxicity. However, the role of CD73/adenosine signaling in the tumor and normal tissue responses to radiotherapy and its use as therapeutic target to improve the outcome of radiotherapy approaches is less understood. The present review will highlight the dual role of CD73 and adenosine in tumor and tissue responses to radiotherapy with a special focus to the lung. It will also discuss the potential benefits and risks of pharmacologic modulation of the CD73/adenosine system to increase the therapeutic gain of radiotherapy or combined radioimmunotherapy in cancer treatment.

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Section: Dual Face Of Radiation-induced Immune Changes: Balance Betwementioning

confidence: 99%

Targeting the Immunomodulatory CD73/Adenosine System to Improve the Therapeutic Gain of Radiotherapy

2019

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“…Finally, radiation-induced stress or damage in the tumor itself results in several phenotypic changes. By secreting cytokines, chemokines or growth factors, as well as up-regulating specific surface receptors, e.g., PD-L1, CTLA-4, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and others, tumor cells become competent in dampening and finally escaping the immune system (Figure 1) [79,80,81,82,83,84]. Several therapeutic strategies aim at the inhibition of such tumor cell-extrinsic factors that lead to primary and adaptive resistance and will be addressed in more detail in the “Immunotherapy in lung cancer” section, but have also been nicely reviewed by others [24,30].…”

Section: Radiotherapy In the Thoracic Region—tumor Control Versus mentioning

confidence: 99%

Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

Wirsdörfer

Leve

Jendrossek

2018

IJMS

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In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.

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“…It serves as a sophisticated signalling molecule which participates in regulating a variety of cellular activities [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]. A vital role for CEACAM1, the only member of the CEA family found on monocytes [24], [25], in the survival and function of monocytes has been suggested; and CEACAM1-dependent regulation of primary CD14+ monocyte survival and control of angiogenesis in a murine inflammation model has also been reported [16], [24].…”

Section: Introductionmentioning

confidence: 99%

Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype

et al. 2014

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Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether Moraxella catarrhalis Ubiquitous Surface Protein A1 (UspA1), known to bind to a widely expressed human cell surface receptor CEACAM1, influences monocyte differentiation as receptor engagement has been shown to have profound effects on monocytes. We used the recombinant molecules corresponding to the regions of UspA1 which either bind (rD-7; UspA1527–665) or do not bind (r6–8; UspA1659–863) to CEACAM1 and investigated their effects on CD206, CD80 and CD86 expression on freshly isolated human CD14+ monocytes from peripheral blood mononuclear cells (PBMC). Exposure to rD-7, but not r6–8, biased monocyte differentiation towards a CD14+CD206+ phenotype, with reduced CD80 expression. Monocytes treated with rD-7 also secreted high levels of IL-1ra and chemokine IL-8 but not IL-10 or IL-12p70. The effects of rD-7 were independent of any residual endotoxin. Unexpectedly, these effects of rD-7 were also independent of its ability to bind to CEACAM1, as monocyte pre-treatment with the anti-CEACAM antibody A0115 known to inhibit rD-7 binding to the receptor, did not affect rD-7-driven differentiation. Further, another control protein rD-7/D (a mutant form of rD-7, known not to bind to CEACAMs), also behaved as the parent molecule. Our data suggest that specific regions of M. catarrhalis adhesin UspA1 may modulate inflammation during infection through a yet unknown receptor on monocytes.

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CEACAM1 : modulateur central du métabolisme, de la progression tumorale,de l’angiogenèse et de l’immunité

Cited by 7 publications

References 29 publications

Targeting the Immunomodulatory CD73/Adenosine System to Improve the Therapeutic Gain of Radiotherapy

Targeting the Immunomodulatory CD73/Adenosine System to Improve the Therapeutic Gain of Radiotherapy

Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype

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