Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press144110.17650/1726-9776-2021-17-1-167-177REVIEWОБЗОРAtlantis exploration: predictive biomarkers to immunotherapy responseВ поисках Атлантиды: предиктивные биомаркеры ответа на иммунотерапиюhttps://orcid.org/0000-0003-3850-7109NosovA. K.НосовА. К.
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68.

https://orcid.org/0000-0002-5590-8804KrotovN. F.КротовН. Ф.
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68.

https://orcid.org/0000-0002-6276-1716BerkutM. V.БеркутМ. В.
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.

Беркут Мария Владимировна.

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68.

Department of Oncourology, N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaХирургическое отделение онкоурологии ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России060520211711671770405202104052021https://oncourology.abvpress.ru/oncur/article/view/1441

The emergence and continuous development of immune checkpoint inhibitors (ICIs) therapy brings a revolution in cancer therapy history including urothelial carcinoma. Early accurate targeting and adequate treatment are critical to patient prognosis and overall survival. To overcome these limitations, two strategies are actively being pursued: identification of predictive biomarkers for clinical response to ICIs and multi-pronged combination therapies. Biomarkers might allow clinicians to practice a precision medicine approach in ICIs (biomarkerbased patient selection). The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities, and guide combination approaches.

The greatest focus in clinical trials and reviews has been on tumor-cell PD-L1 expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. In this review, we discuss the status of PD-L1 testing and explore emerging data on new biomarker strategies with tumor-infiltrating lymphocytes, mutational burden, immune gene signatures, microsatellite instability and molecular subtypes.

Появление и постоянное развитие терапии с использованием ингибиторов иммунных контрольных точек (ICI) совершили революцию в истории лечения рака, в том числе уротелиальной карциномы. Ранний точный подбор мишени и адекватное лечение имеют решающее значение для прогноза заболевания и продолжительности общей выживаемости. Для преодоления этих ограничений активно используются 2 стратегии: идентификация прогностических биомаркеров для клинического ответа при ICI-терапии и пролонгированная комбинированная терапия. Биомаркеры могут позволить клиницистам практиковать подходы прецизионной медицины при назначении ICI-терапии (отбор пациентов на основе биомаркеров).

Наибольшее внимание в клинических испытаниях и обзорах уделяется экспрессии PD-L1 в опухолевых клетках. Несмотря на то что случаи уротелиального рака с положительной экспрессией PD-L1 могут иметь потенциальную выгоду при назначении иммунотерапии, одного тестирования PD-L1 недостаточно для отбора пациентов при большинстве злокачественных новообразований. В данном обзоре мы обсуждаем статус тестирования PD-L1 и представляем новые данные о потенциальных предиктивных биомаркерах при назначении ICI-терапии: факторы противоопухолевого иммунитета, мутационную нагрузку и сигнатуры генов, микросателлитную нестабильность и молекулярные подтипы рака мочевого пузыря.

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