The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity

Mbongue, Jacques C.; Nicholas, Dequina; Torrez, Timothy; Kim, Nan-Sun; Firek, Anthony; Langridge, William H. R.

doi:10.3390/vaccines3030703

Cited by 300 publications

(258 citation statements)

References 152 publications

(266 reference statements)

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“…Not all immune checkpoint or immunomodulatory molecules take the form of a receptor or ligand. Some may be expressed by the cell in a free soluble form, such as indoleamine 2,3-dioxygenase (IDO1), an enzyme produced by some activated macrophages and also overexpressed by many tumors [94] . The enzyme depletes tryptophan in the microenvironment, with production of the catabolite kynurenine, which harms the cytotoxic T-cells.…”

Section: Antibodies To Immune Checkpoint Moleculesmentioning

confidence: 99%

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Oiseth¹,

Aziz²

2017

JCMT

275

199

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The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus CalmetteGuérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the "biologic passport" of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1. Key words:Cancer immunotherapy, immune checkpoint inhibitors, PD-1, programmed death-ligand 1, cytotoxic T-lymphocyte-associated antigen-4, adoptive cell therapy, cancer vaccines, oncolytic viruses, history of cancer immunology ABSTRACTArticle history:

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Section: Antibodies To Immune Checkpoint Moleculesmentioning

confidence: 99%

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Oiseth¹,

Aziz²

2017

JCMT

275

199

View full text Add to dashboard Cite

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“…IDO is the first and rate-limiting enzyme in the pathway that degrades the essential amino acid tryptophan to kynurenine (27). The function of IDO has been best characterized in tumor immunology.…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Sharma

Dalmazi

Caturegli

2016

Thyroid

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Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2 h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. Conclusions: This study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2 h4 mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade.

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“…Стимуляция через TLR3 и TLR4 индуцирует экспрессию IDO в ДК, а сти-муляция через TLR7/8 -в моноцитах. Лигация TLR3/4 через канонический путь стимуляции NF-kB с участием фактора транскрипции IRF3 (interferon regulatory factor) индуцирует синтез TNFα и IFNβ, которые в дальнейшем и стиму-лируют экспрессию IDO [40]. При этом TNFα на уровне экспрессии гена IDO оказывает сти-мулирующий эффект на индуцирующее влияние IFNγ [62].…”

Section: немного про Indoleamine-23-dioxygenase (Ido)unclassified

“…IDO1 и IDO2. Гены послед-них двух ферментов располагаются тандемом на хромосоме 8р21, являясь структурно и эво-люционно родственными белками [40]. Впер-вые антипролиферативный эффект IDO (42kD мономерный протеин) в отношении бактерий, простейших и опухолевых клеток был описан в 1984 г.…”

unclassified

Tryptophan and Indoleamine-2,3-Dioxygenase (Ido) in Pathogenesis of Immunosuppressive Clinical Conditions

Козлов¹,

Демина²

2017

Med. immunol.

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Адрес для переписки:Козлов Владимир Александрович ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии» 630099, Россия, г. Новосибирск, ул. Ядринцевская, 14. Тел.: 8 (383) 222-66-27. Факс: 8 (383) 222-70-28. E-mail: vakoz40@yandex.ru Address for correspondence : Kozlov Vladimir A. Research Institute of Fundamental and Clinical Immunology 630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., Образец цитирования: иммунология, 2017. Т. 19, № 3. С. 225-240. doi: 10.15789/1563-0625-2017-3-225-240 © Козлов В.А., Демина Д.В., 2017 For citation: V. A. Kozlov, Immunologiya, 2017, Vol. 19, no. 3, pp. 225-240. doi: 10.15789/1563-0625-2017-3-225-240 DOI: 10.15789/1563-0625-2017 ТРИПТОФАН И INDOLEAMINE-2,3-DIOXYGENASE (IDO) В ПАТОГЕНЕЗЕ ИММУНОКОМПРОМЕТИРОВАННЫХ ЗАБОЛЕВАНИЙКозлов В.А., Демина Д.В. ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии», г. Новосибирск, РоссияРезюме. Все больше и больше литературных данных свидетельствуют о ведущей роли в форми-ровании иммуносупрессорных механизмов фермента indoleamin 2,3-deoxygenase (IDO), которая продуцируется в основном дендритными клетками, в индукции которой участвует в основном IFNγ и функции которой состоят в индукции катаболизма незаменимой аминокислоты триптофана. Уже одно снижение уровня триптофана в околоклеточной среде обуславливает подавление ряда функ-ций клеток иммунной системы и индукцию регуляторных Т-клеток. Появление ряда катаболитов триптофана еще более усугубляет иммунодепрессивное состояние, индуцированное повышенной экспрессией IDO. Предполагается, что цепочка из IDO, триптофана и его катаболитов в значитель-ной степени определяет формирование гиперсупрессорного состояния при опухолевом росте и гипо-(или недостаточного) супрессорного состояния при аутоиммунных и аллергических заболеваниях. Отсюда вытекают и новые задачи в терапии: найти способы терапии, направленные на снижение ак-тивности фермента IDO, участвующего в индукции клеток-супрессоров при опухолевом росте, и в то же время направленные на стимуляцию активности данного фермента для повышения супрессорной активности регуляторных клеток. that the interactions between IDO, tryptophan and its catabolites largely determine a development of hypersuppressor state in tumor growth and a hypo-(or lack of) suppressor status in autoimmune and allergic diseases. This implies some novel tasks for the therapy, including a treatment aimed for reduction of the IDO activity since the latter is involved in suppressor cell induction during tumor growth. Respectively, stimulation of IDO activity may augment suppressor activity of the regulatory cells. Ключевые слова: иммунопатология, иммуносупрессия, триптофан, indoleamine 2,3-dioxygenase, кинуренин TRYPTOPHAN AND INDOLEAMINE-2,3-DIOXYGENASE (IDO) IN PATHOGENESIS OF IMMUNOSUPPRESSIVE CLINICAL CONDITIONS

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The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity

Cited by 300 publications

References 152 publications

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Tryptophan and Indoleamine-2,3-Dioxygenase (Ido) in Pathogenesis of Immunosuppressive Clinical Conditions

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