ketendoКлиническая и экспериментальная тиреоидологияClinical and experimental thyroidology1995-54722310-3787Endocrinology Research Centre10.14341/ket9875ketendo-9875Research ArticleОбзоры литературыReview of literatureПоражение желез внутренней секреции как осложнение иммунотерапии в практике онкологаLesions in endocrine glands as a complication of immunotherapy in the practice of oncologisthttps://orcid.org/0000-0001-6876-3336НуралиеваНурана ФейзуллаевнаNuralievaNurana F.Dr.NuralievaNF@yandex.ruhttps://orcid.org/0000-0002-8520-8702ТрошинаЕкатерина АнатольевнаTroshinaEkaterina A.

д.м.н., профессор, член-корр. РАН

MD, PhD, Professor

troshina@inbox.ruhttps://orcid.org/0000-0002-5634-7877МельниченкоГалина АфанасьевнаMelnichenkoGalina A.

д.м.н., профессор, академик РАН

MD, PhD, Professor

teofrast2000@mail.ru<p>ФГБУ &ldquo;Национальный медицинский исследовательский центр эндокринологии&rdquo;</p>Россия<p>Endocrinology Research Centre</p>Russian Federation<p>ФГБУ &laquo;Национальный медицинский исследовательский центр эндокринологии&raquo;</p>Россия<p>Endocrinology Research Centre</p>Russian Federation201819042019144174182Copyright &#x00A9; Нуралиева Н.Ф., Трошина Е.А., Мельниченко Г.А., 20182018Нуралиева Н.Ф., Трошина Е.А., Мельниченко Г.А.Nuralieva N.F., Troshina E.A., Melnichenko G.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cet-endojournals.ru/jour/article/view/9875

В представленном обзоре описаны поражения эндокринной системы, возникающие вследствие иммунотерапии онкологических заболеваний. Этот феномен связан с ингибированием препаратами моноклональных антител контрольных точек, которые не позволяют иммунной системе воздействовать на опухолевые клетки: CTLA4, PD-1 и PD-L1. Применение данной группы лекарственных средств позволяет увеличить продолжительность жизни пациентов с онкологическими заболеваниями, однако может также приводить к развитию аутоиммунных эндокринопатий (тиреоидиту, адреналиту, сахарному диабету, гипофизиту), которые нередко манифестируют жизнеугрожающими состояниями. С учетом вышесказанного обсуждается необходимость регулярного контроля функции органов-мишеней на фоне иммунотерапии злокачественных новообразований.

В то же время феномен развития аутоиммунных эндокринопатий на фоне терапии ингибиторами иммунологических контрольных точек представляет фундаментальный интерес для эндокринологов. Ятрогенные поражения эндокринной системы являются уникальными моделями инициации иммунной аутоагрессии. Так, развитие адреналита на фоне терапии ингибитором PD-1 предполагает, что PD-1 вовлечен в патогенез аутоиммунной надпочечниковой недостаточности и у больных, не получающих лечение данным препаратом. Таким образом, требуется уточнение роли PD-1 в развитии адреналита. Результаты подобных исследований позволят идентифицировать группы риска и соответственно своевременно диагностировать аутоиммунную надпочечниковую недостаточность и начать лечение.

This review describes the lesions of the endocrine system that occur as a result of immunotherapy of cancer. This phenomenon is associated with the inhibition by monoclonal antibodies of checkpoints, which do not allow the immune system to affect tumor cells: CTLA-4, PD-1 and PD-L1. Immunotherapy by this group of drugs allows to increase the life expectancy of patients with cancer, but it also leads to the development of autoimmune endocrinopathies (thyroiditis, adrenalitis, diabetes mellitus, hypophysitis), which often manifest by life-threatening conditions. In view of the above, the necessity to carry out regular monitoring of the function of target organs in patients receiving immunotherapy for malignant tumors is discussed.

On the other hand, the phenomenon of developing the autoimmune endocrinopathies during therapy with immunological checkpoints inhibitors is of fundamental interest to endocrinologists. Iatrogenic lesions of the endocrine system are unique models of initiation of immune autoagression. Thus, the development of adrenalitis in patients receiving treatment with a PD-1 inhibitor suggests that the PD-1 is involved in the pathogenesis of autoimmune adrenal insufficiency in patients not receiving treatment with this drug. Thus, clarification of the role of PD-1 in the development of adrenalitis is required. The results of such investigations will allow to identify the risk groups for the development of autoimmune adrenal insufficiency and, accordingly, timely diagnosing it and beginning treatment.

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The authors declare that there are no conflicts of interest present.