Mechanisms of tumour escape from immune surveillance

Lisiecka, Urszula; Kostro, K.

doi:10.1515/jvetres-2016-0068

Cited by 15 publications

(8 citation statements)

References 51 publications

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“…Various mechanisms explaining the immune escape have been proposed, including immune editing, targeting regulatory T‐cell function, antigen presentation, modification of immunosuppressive mediators, tolerance and immune deviation, and apoptosis of cytotoxic T cells. While recognizing the complexities of and interactions between these various mechanisms, I shall focus here on the role of the Kyn metabolite precursor Trp in immune escape and, in particular, Trp availability to tumors and its physiological determinants will be identified and means of limiting this availability will be proposed.…”

Section: Introductionmentioning

confidence: 99%

Targeting tryptophan availability to tumors: the answer to immune escape?

Badawy

2018

Immunol Cell Biol

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Tumoral immune escape is an obstacle to successful cancer therapy. Tryptophan (Trp) metabolites along the kynurenine pathway induce immunosuppression involving apoptosis of effector immune cells, which tumors use to escape an immune response. Production of these metabolites is initiated by indoleamine 2,3-dioxygenase (IDO1). IDO1 inhibitors, however, do not always overcome the immune escape and another enzyme expressed in tumors, Trp 2,3-dioxygenase (TDO2), has been suggested as the reason. However, without Trp, tumors cannot achieve an immune escape through either enzyme. Trp is therefore key to immune escape. In this perspective paper, Trp availability to tumors will be considered and strategies limiting it proposed. One major determinant of Trp availability is the large increase in plasma free (non-albumin-bound) Trp in cancer patients, caused by the low albumin and the high non-esterified fatty acid (NEFA) concentrations in plasma. Albumin infusions, antilipolytic therapy or both could be used, if indicated, as adjuncts to immunotherapy and other therapies. Inhibition of amino acid uptake by tumors is another strategy and α-methyl-DL-tryptophan or other potential inhibitors could fulfill this role. Glucocorticoid receptor antagonists may have a role in preventing glucocorticoid induction of TDO in host liver and tumors expressing it and in undermining the permissive effect of glucocorticoids on IDO1 induction by cytokines. Nicotinamide may be a promising TDO2 inhibitor lacking disadvantages of current inhibitors. Establishing the Trp disposition status of cancer patients and in various tumor types may provide the information necessary to formulate tailored therapeutic approaches to cancer immunotherapy that can also undermine tumoral immune escape.

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Section: Introductionmentioning

confidence: 99%

Targeting tryptophan availability to tumors: the answer to immune escape?

Badawy

2018

Immunol Cell Biol

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“…However, in breast cancer patients the relationship between PD-L1 expression and prognosis remains unclear. Some studies have shown that positive PD-L1 was associated with significantly poor survival (Lisiecka and Kostro, 2016), but other studies could not confirm these findings ( Park et al, 2016). These discrepancies may be due to different thresholds were used to determine expression positivity and because the studies included populations of different races.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it has become very clear that malignant cells must be able to successfully evade immune surveillance to progress and metastasis. Tumor cells use a variety of different pathways to achieve this goal (Lisiecka and Kostro , 2016).…”

Section: Discussionmentioning

confidence: 99%

The Programmed Death-1 Receptor, Programmed Death-1 Ligand (PD-1/PD-L1) and Apoptosis in Breast Cancer Patients: A potential Mechanism of Immune Escape

Abdel-hamied

El-Sheredy

Fadali

et al. 2020

International Journal of Cancer and Biomedical Research

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Background: Interaction between programmed cell death ligand-1 (PD-L1) and its receptor PD-1 is a major inhibitory pathway in maintaining an immunosuppressive tumor microenvironment. The expression of PD-L1 in various solid tumors is proposed to function in preventing T-cell mediated tumor killing, and activating tumor -suppressive cell populations through different mechanisms. The B-cell Lymphoma-2 (Bcl-2) is a key anti-apoptotic protein has been described as mediators of cancer progression. The expression of PD-L1 on activated T-cells supports their survival. Objectives: Evaluate the expression of PD-1, PD-L1 in relation to apoptosis among patients with breast cancer. All parameters were correlated with each other and with the clinicopathological features of the disease. Patients and Methods: This case-control study was conducted on 55 breast cancer patients with different stages of the disease. In addition, 20 age-matched normal healthy individuals were included in the study as a control group. Patient groups divided into early stage disease and advanced stage disease. The percentage of PD-1 and PDL-1 were measured in blood samples of all subjects using flowcytometry. Quantitative detection of Bcl-2 protein was assessed using enzyme linked immunosorbent assay. Results: PD-L1 expression was significantly associated with tumor grade, lymph node involvement, tumor size, vascular invasion and negative hormonal receptors. PD-1 expression was significantly associated only with lymph-node involvement. A significant positive correlation was existed between serum Bcl-2 and PD-L1+ expressing granulocytes. Conclusions: The direct correlation between PD-L1+ expression and serum Bcl-2 concentration may explore a role of apoptotic machinery in the pathogenesis of breast cancer.

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“…Nevertheless, tumor cells can get away from body immune superintendence when changing their biological properties. The functions of immune factors in the incidence, progression, and healing of tumor has provided great interest in immunology of tumor and immunotherapy of cancer (Lisiecka and Kostro, 2016[ 56 ]; Mohme et al, 2017[ 66 ]). Several therapeutic approaches have designed to attack tumors directly.…”

Section: Introductionmentioning

confidence: 99%