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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Immunology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Immunology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский иммунологический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1028-7221</issn><issn publication-format="electronic">2782-7291</issn><publisher><publisher-name xml:lang="en">Russian Society of Immunology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">17309</article-id><article-id pub-id-type="doi">10.46235/1028-7221-17309-APF</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Unknown</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Anti-PD-1 for the treatment of advanced cutaneous squamous cell carcinoma: a systematic review and meta-analysis</article-title><trans-title-group xml:lang="ru"><trans-title>Ингибиторы PD-1 в терапии агрессивных форм плоскоклеточного рака кожи: систематический обзор и мета-анализ</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Hashemzehi</surname><given-names>Ameneh</given-names></name><name xml:lang="ru"><surname>Хашемзехи</surname><given-names>А.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Faculty of veterinary medicine, Islamic Azad University, Kazeroon, Iran.</p></bio><bio xml:lang="ru"><p>Факультет ветеринарной медицины, Исламский университет Азад, Казерун, Иран. </p></bio><email>Hashemzehiameneh@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shirali</surname><given-names>Fatemeh</given-names></name><name xml:lang="ru"><surname>Ширали</surname><given-names>Ф.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>School of Medicine, Ahvaz Jondi Shapour University of Medical Sciences, Ahvaz, Iran.</p></bio><bio xml:lang="ru"><p>Школа медицины, Медицинский университет Ахваз Ионди Шапур, Ахваз, Иран.</p></bio><email>Fatishirali12345@gmail.com</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Norooziseyedhosseini</surname><given-names>Hanieh</given-names></name><name xml:lang="ru"><surname>Норузисейедхоссейни</surname><given-names>Х.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya Street, Moscow 119991, Russian Federation.</p></bio><bio xml:lang="ru"><p>Первый Московский государственный университет им. И.Сеченова, Москва, Россия. </p></bio><email>H1996norozi@gmail.com</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Imani</surname><given-names>Roya</given-names></name><name xml:lang="ru"><surname>Имани</surname><given-names>Р.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya Street, Moscow 119991, Russian Federation.</p></bio><bio xml:lang="ru"><p>Первый Московский государственный университет им. И.Сеченова, Москва, Россия. </p></bio><email>roz_im74@yahoo.com</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shahrava</surname><given-names>Dorsa Sadat</given-names></name><name xml:lang="ru"><surname>Шахрава</surname><given-names>Д. С.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Department of Biology, Faculty of Basic sciences, Roudehen Branch, Islamic Azad University, Roudehen, Iran.</p></bio><bio xml:lang="ru"><p>Школа медицины Гилянский медицинский университет, Гилян, Решт, Иран. </p></bio><email>dorsashahrava@gmail.com</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Nadem</surname><given-names>Javad</given-names></name><name xml:lang="ru"><surname>Надем</surname><given-names>Й.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.</p></bio><bio xml:lang="ru"><p>Исламский медицинский университет Азад, отделение Решт, Решт, Иран. </p></bio><email>javad.n.c@gmail.com</email><xref ref-type="aff" rid="aff5"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Hoseinpour</surname><given-names>Faezeh</given-names></name><name xml:lang="ru"><surname>Хосейнпур</surname><given-names>Ф.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Islamic Azad University of Medical Science Qeshm International Branch, Qeshm, Iran.</p></bio><bio xml:lang="ru"><p>Исламский медицинский университет Азад, отделение Решт, Решт, Иран.</p></bio><email>Niloofar.deravi@hotmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Hataminia</surname><given-names>Javad</given-names></name><name xml:lang="ru"><surname>Хатаминиа</surname><given-names>Й.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.</p></bio><bio xml:lang="ru"><p>Научный студенческий комитет, факультет медицины, Медицинский университет Гормозган, Бендер-Аббас, Иран. </p></bio><email>hataminiajavad@gmail.com</email><xref ref-type="aff" rid="aff6"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Salimi</surname><given-names>Omid</given-names></name><name xml:lang="ru"><surname>Салими</surname><given-names>О.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran.</p>
<p>Student research committee, Na.C., Islamic Azad University, Najafabad, Iran</p></bio><bio xml:lang="ru"><p>Отдел медицины, Научный студенческий комитет, Исламский университет, Иран. </p></bio><email>salimiomid953@gmail.com</email><xref ref-type="aff" rid="aff7"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Amini</surname><given-names>Alireza</given-names></name><name xml:lang="ru"><surname>Амини</surname><given-names>А.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran. Student research committee, Na.C., Islamic Azad University, Najafabad, Iran</p></bio><bio xml:lang="ru"><p>Научный студенческий комитет, Исламский университет, Иран</p></bio><email>alirezaamini031k@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ghorbani Sharif</surname><given-names>Amirali</given-names></name><name xml:lang="ru"><surname>Гхорбани Шариф</surname><given-names>А.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.</p></bio><bio xml:lang="ru"><p>Факультет медицины, Исламский университет Азад, Тегеран, Иран. </p></bio><email>aghorbanisharif@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Hadimaleki</surname><given-names>Sepideh</given-names></name><name xml:lang="ru"><surname>Хадималеки</surname><given-names>С.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Department of Pathology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.</p></bio><bio xml:lang="ru"><p>Отдел патологии, Больница Имама Реза, Медицинский университет Тавриза, Тавриз, Тегеран. </p></bio><email>sepidhadi74@gmail.com</email><xref ref-type="aff" rid="aff8"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Rahimi</surname><given-names>Benyamin</given-names></name><name xml:lang="ru"><surname>Рахими</surname><given-names>Б.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Department of Urology, Imam Reza Hospital, Tabriz University of Medical Science, Tabriz, Iran.</p></bio><bio xml:lang="ru"><p>Отдел урологии, Больница Имама Реза, Медицинский университет Тавриза, Тавриз, Тегеран.</p></bio><email>rahimi_benyamin@yahoo.com</email><xref ref-type="aff" rid="aff8"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Naziri</surname><given-names>Mahdyieh</given-names></name><name xml:lang="ru"><surname>Назири</surname><given-names>М.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Students Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.</p></bio><bio xml:lang="ru"><p>Научный студенческий комитет, Школа медицины, Иранский медицинский университет, Тегеран, Иран. </p></bio><email>nazirimahdyieh@yahoo.com</email><xref ref-type="aff" rid="aff9"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Deravi</surname><given-names>Niloofar</given-names></name><name xml:lang="ru"><surname>Дерави</surname><given-names>Н.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Students Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran</p></bio><bio xml:lang="ru"><p>Научный студенческий комитет, Школа медицины, Медицинский университет Шахид Бехешти, Тегеран, Иран</p></bio><email>niloofar.deravi@gmail.com</email><xref ref-type="aff" rid="aff10"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Mehrasa</surname><given-names>Parisa</given-names></name><name xml:lang="ru"><surname>Мехраза</surname><given-names>П.</given-names></name></name-alternatives><address><country country="IR">Iran, Islamic Republic of</country></address><bio xml:lang="en"><p>Assistant Professor of Pathology, Department of Pathology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.</p></bio><bio xml:lang="ru"><p>Ассистент кафедры патологии, Отдел патологии, школа медицины , Медицинский университет Табриза, Тавриз, Иран. </p></bio><email>Parisamehrasa@yahoo.com</email><xref ref-type="aff" rid="aff8"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Islamic Azad University, Kazeroon, Iran</institution></aff><aff><institution xml:lang="ru">Исламский университет Азад, Казерун, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Ahvaz Jondi Shapour University of Medical Sciences, Ahvaz, Iran</institution></aff><aff><institution xml:lang="ru">Медицинский университет Ахваз Ионди Шапур, Ахваз, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный университет им. И.Сеченова, Москва, Россия</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Roudehen Branch, Islamic Azad University, Roudehen, Iran</institution></aff><aff><institution xml:lang="ru">Отделение Роудехен, Исламский университет Азад, Роудехен, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff5"><aff><institution xml:lang="en">Guilan University of Medical Sciences, Rasht, Iran</institution></aff><aff><institution xml:lang="ru">Гилянский медицинский университет, Гилян, Решт, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff6"><aff><institution xml:lang="en">Hormozgan University of Medical Sciences, Bandar Abbas, Iran</institution></aff><aff><institution xml:lang="ru">Медицинский университет Гормозган, Бендер-Аббас, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff7"><aff><institution xml:lang="en">Islamic Azad University, Najafabad, Iran</institution></aff><aff><institution xml:lang="ru">Исламский университет Азад, Казерун, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff8"><aff><institution xml:lang="en">Tabriz University of Medical Sciences, Tabriz, Iran</institution></aff><aff><institution xml:lang="ru">Медицинский университет Табриз, Табриз, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff9"><aff><institution xml:lang="en">Iran University of Medical Sciences, Tehran, Iran</institution></aff><aff><institution xml:lang="ru">Иранский медицинский университет, Тегеран, Иран</institution></aff></aff-alternatives><aff-alternatives id="aff10"><aff><institution xml:lang="en">Shahid Beheshti University of Medical Sciences, Tehran, Iran</institution></aff><aff><institution xml:lang="ru">Медицинский университет Шахид Бехешти, Тегеран, Иран</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-09-25" publication-format="electronic"><day>25</day><month>09</month><year>2025</year></pub-date><history><date date-type="received" iso-8601-date="2025-09-12"><day>12</day><month>09</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-09-24"><day>24</day><month>09</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; , Hashemzehi A., Shirali F., Norooziseyedhosseini H., Imani R., Shahrava D., Nadem J., Hoseinpour F., Hataminia J., Salimi O., Amini A., Ghorbani Sharif A., Hadimaleki S., Rahimi B., Naziri M., Deravi N., Mehrasa P.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; , Hashemzehi A., Shirali F., Norooziseyedhosseini H., Imani R., Shahrava D., Nadem J., Hoseinpour F., Hataminia J., Salimi O., Amini A., Ghorbani Sharif A., Hadimaleki S., Rahimi B., Naziri M., Deravi N., Mehrasa P.</copyright-statement><copyright-holder xml:lang="en">Hashemzehi A., Shirali F., Norooziseyedhosseini H., Imani R., Shahrava D., Nadem J., Hoseinpour F., Hataminia J., Salimi O., Amini A., Ghorbani Sharif A., Hadimaleki S., Rahimi B., Naziri M., Deravi N., Mehrasa P.</copyright-holder><copyright-holder xml:lang="ru">Hashemzehi A., Shirali F., Norooziseyedhosseini H., Imani R., Shahrava D., Nadem J., Hoseinpour F., Hataminia J., Salimi O., Amini A., Ghorbani Sharif A., Hadimaleki S., Rahimi B., Naziri M., Deravi N., Mehrasa P.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://rusimmun.ru/jour/article/view/17309">https://rusimmun.ru/jour/article/view/17309</self-uri><abstract xml:lang="en"><p>Advanced cutaneous squamous cell carcinoma (CSCC) is a formidable cancer with historically constrained systemic therapy alternatives. Immune checkpoint drugs that target programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have surfaced as viable treatments. This revised systematic review and meta-analysis sought to assess the effectiveness of anti-PD-1/PD-L1–based therapy in advanced CSCC. <bold>Methods: </bold>A thorough search of PubMed, Scopus, and Web of Science was performed till August 12, 2025. Eligible studies comprised clinical trials and observational cohorts that reported the objective response rate (ORR) in patients with advanced CSCC treated with anti-PD-1/PD-L1 drugs. Pooled estimates were derived utilizing a random-effects model with limited maximum likelihood (REML) estimation. Heterogeneity was evaluated using Cochran’s Q, I², and τ². Subgroup analyses were conducted based on drug regimen, geographic location, and study design. Publication bias was assessed by funnel plots and Egger’s regression analysis. <bold>Results: </bold>Forty-eight studies involving 4,172 patients met the inclusion criteria. The pooled ORR was 0.51 (95% CI, 0.46–0.55; z = 21.21, p &lt; 0.001) with substantial heterogeneity (I² = 89.13%). Subgroup analyses showed ORRs ranging from 0.21 to 0.73 by drug regimen, with cemiplimab plus pembrolizumab achieving the highest response rates. Geographic location (p = 0.014, R² = 14.52%) and study design (p = 0.002, R² = 16.84%) were significantly associated with treatment effect, while drug type alone was not (p = 0.679). Egger’s test indicated small-study effects (p = 0.0174). <bold>Conclusion: </bold>Anti-PD-1/PD-L1 therapy demonstrates meaningful clinical activity in advanced CSCC, achieving responses in approximately half of treated patients. Geographic and methodological factors contribute to outcome variability, underscoring the need for large, biomarker-driven trials to refine patient selection and optimize therapeutic benefit.</p></abstract><trans-abstract xml:lang="ru"><p>Диссеминированная плоскоклеточная карцинома кожи (ДККК) — это грозное онкологическое заболевание с ограниченными опциями системной терапии. Препараты, воздействующие на контрольные точки иммунитета, такие как, ингибиторы PD-1 и PD-L1 (программируемая клеточная гибель- тип 1), стали перспективными методами лечения. Целью данного ревизованного систематического обзора и метаанализа было оценить эффективность терапии на основе анти-PD-1/PD-L1 при распространенной ДККК. Методы: Был проведен тщательный поиск в базах данных PubMed, Scopus и Web of Science по 12 августа 2025 года. В исследование были включены клинические испытания и наблюдательные когорты, в которых были сведения об объективной частоте ответа (ОРР) у пациентов с распространенной ДККК, получавших лечение препаратами анти-PD-1/PD-L1. Объединенные оценки были получены с использованием модели случайных эффектов с ограниченной оценкой максимального правдоподобия (REML). Гетерогенность оценивалась с использованием критериев Кохрана Q, I² и τ². Анализ подгрупп проводился с учетом схемы лечения, географической локации и дизайна исследования. Неопределенность результатов оценивалось с помощью диаграмм рассеяния и регрессионного анализа Эггера. Результаты: По критериям включения отобраны 48 исследований с участием 4172 пациентов. Объединенный показатель объективного ответа составил 0,51 (95% ДИ, 0,46–0,55; z = 21,21, p &lt; 0,001) со значительной гетерогенностью (I² = 89,13%). Анализ подгрупп показал, что показатели объективного ответа варьировали от 0,21 до 0,73 в зависимости от схемы лечения, при этом для цемиплимаба в сочетании с пембролизумабом показаны наиболее высокие уровни терапевтического ответа. Географическая локация исследований (p = 0,014, R² = 14,52%) и их дизайн (p = 0,002, R² = 16,84%) были значимо связаны с эффектом лечения, в то время как тип препарата сам по себе не был связан с ним (p = 0,679). Тест Эггера показал эффекты малых выборок в исследованиях (p = 0,0174). Выводы: Терапия анти-PD-1/PD-L1 демонстрирует значимую клиническую активность при распространенном плоскоклеточном раке кожи, достигая ответа примерно у половины пролеченных пациентов. Географические и методологические факторы влияют на вариабельность результатов, подчеркивая необходимость проведения крупных исследований, основанных на биомаркерах, для уточнения критериев отбора пациентов и оптимизации терапевтического эффекта.</p></trans-abstract><kwd-group xml:lang="en"><kwd>cutaneous carcinoma</kwd><kwd>immune checkpoints</kwd><kwd>PD-1</kwd><kwd>PD-L1</kwd><kwd>inhibitors</kwd><kwd>review</kwd><kwd>meta-analysis</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>кожная карцинома</kwd><kwd>иммунные контрольные точки</kwd><kwd>PD-1</kwd><kwd>PD-L1</kwd><kwd>ингибиторы</kwd><kwd>обзор</kwd><kwd>мета-анализ</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Fania L, Didona D, Di Pietro FR, Verkhovskaia S, Morese R, Paolino G, Donati M, Ricci F, Coco V, Ricci F, Candi E, Abeni D, Dellambra E. Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches. 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