OSTEOSARKOMADA IMMUN MIKRO-MUHIT: PROGNOZ VA TERAPEVTIK JAVOBNI BELGILOVCHI OMILLAR BO‘YICHA ZAMONAVIY SHARH
- Авторы:G‘afur-Oxunov Mirza Allayorovich, Sabirov Djaxongir Ruziyevich, Iskandarov Kamol Zayniddinovich
- Дата публикации:July 9, 2026
- Тип:Статья
- DOI: 10.64156/mju.9449 Скопировано
- Том / № Выпуска:Том 1 №4 (2026)
Аннотация
Annotatsiya. Tadqiqot maqsadi. 2019–2026 yillardagi adabiyotlar asosida osteosarkomada immun mikro-muhitning tarkibi, funksional holati va fazoviy arxitekturasi prognoz hamda terapevtik javobni qanday belgilashini tahlil qilish.
Materiallar va usullar. Scopus, Web of Science va PubMed bazalarida osteosarkoma, immune microenvironment, PD-L1, CD8, T-cell exhaustion, single-cell RNA sequencing, spatial transcriptomics va immunotherapy kalit so‘zlari bo‘yicha zamonaviy klinik qo‘llanmalar, translatsion ishlar, metaanalizlar va II faza tadqiqotlari tanlab olindi.
Xulosa. Osteosarkoma klassik ma’noda to‘liq “immun sovuq” o‘sma emas; u kuchli heterogen, ko‘pincha mioeloid-supressiv va T-hujayra funksiyasi cheklangan immun landshaftga ega. CD8+ va CD4+ limfotsitlarning oddiy miqdoriy bahosi yetarli emas: ularning fazoviy joylashuvi, Treglar bilan nisbati, exhausted fenotipi va PD-1/PD-L1 o‘qi bilan aloqasi prognostik ahamiyatni belgilaydi. Osteosarkomada immun kontekst yakka molekuladan muhimroq bo‘lgani uchun PD-L1, CD8 va CD4 ni integrallashgan morfologik va klinik model tarkibida baholash eng mantiqiy yondashuvdir.
Kalit so‘zlar. Osteosarkoma, immun mikro-muhit, PD-L1, CD8 T-limfotsitlar, T-hujayra charchashi, single-cell transkriptomika, fazoviy transkriptomika, immunoterapiya.
Аннотация. Цель исследования: на основе литературы 2019–2026 годов проанализировать, как состав, функциональное состояние и пространственная архитектура иммунного микроокружения остеосаркомы определяют прогноз и ответ на терапию.
Материалы и методы. В базах Scopus, Web of Science и PubMed по ключевым словам osteosarcoma, immune microenvironment, PD-L1, CD8, T-cell exhaustion, single-cell RNA sequencing, spatial transcriptomics и immunotherapy отобраны современные клинические руководства, трансляционные работы, метаанализы и исследования II фазы.
Заключение. Остеосаркома не является в классическом смысле полностью «иммунологически холодной» опухолью; ей свойствен выраженно гетерогенный, нередко миелоидно-супрессивный иммунный ландшафт с ограниченной функцией Т-клеток. Простой количественной оценки CD8+ и CD4+ лимфоцитов недостаточно: прогностическую значимость определяют их пространственное расположение, соотношение с Treg, истощённый (exhausted) фенотип и связь с осью PD-1/PD-L1. При остеосаркоме иммунный контекст важнее отдельной молекулы, поэтому для прогностической и терапевтической стратификatsiи наиболее логична интегрированная оценка PD-L1, CD8 и CD4 в составе морфологической и клинической модели.
Ключевые слова. Остеосаркома, иммунное микроокружение, PD-L1, CD8 Т-лимфоциты, истощение Т-клеток, одноклеточная транскриптомика, пространственная транскриптомика, иммунотерапия.
Abstract. Purpose of the study: to analyze, based on the 2019–2026 literature, how the composition, functional state and spatial architecture of the osteosarcoma immune microenvironment determine prognosis and therapeutic response.
Materials and methods. Scopus, Web of Science and PubMed were searched using the keywords osteosarcoma, immune microenvironment, PD-L1, CD8, T-cell exhaustion, single-cell RNA sequencing, spatial transcriptomics and immunotherapy; current clinical guidelines, translational studies, meta-analyses and phase II trials were selected.
Conclusion. Osteosarcoma is not uniformly immune-cold; it displays marked heterogeneity, frequently with myeloid suppression and dysfunctional T-cell states. The value of CD8+ and CD4+ infiltrates depends not on density alone but on localization, Treg balance, exhaustion programs and their relationship with PD-1/PD-L1 signaling. Because immune context outweighs any single marker, an integrated tissue model combining PD-L1, CD8 and CD4 is the most informative approach.
Key words: Osteosarcoma, immune microenvironment, PD-L1, CD8 T cells, T-cell exhaustion, single-cell RNA sequencing, spatial transcriptomics, immunotherapy.
References
- Biermann JS, et al. Bone Cancer, Version 2.2025, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2025;23(4):e250017.
- Boye K, et al. Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Cancer Immunol Immunother. 2021;70(9):2617-2624.
- Cao Q, et al. Multiomic analysis reveals the potential of LAG3 as a biomarker in osteosarcoma. 2025. PMC12254381.
- Cheng D, et al. Unraveling T-cell exhaustion in the immune microenvironment of osteosarcoma via single-cell RNA transcriptome. 2024. PMID: 38280005.
- Corre I, et al. The osteosarcoma microenvironment: a complex but targetable ecosystem. Cells. 2020;9(4):976.
- Ding L, et al. Modulating tumor-associated macrophage polarization by anti-MARCO antibody in osteosarcoma. J Orthop Surg Res. 2024;19:453.
- Duan L, et al. Harnessing the immune system against osteosarcoma: from biological understanding to translational opportunity. 2026.
- Hashimoto K, et al. Prognostic meaning of PD-L1 expression in musculoskeletal tumors including osteosarcoma. 2025. PMC11843085.
- Liang G, et al. Nanoparticles targeting the tumor microenvironment for the treatment of osteosarcoma. 2026. PMC12922965.
- Liu Y, et al. Paired pre- and post-chemotherapy single-cell atlas of the osteosarcoma tumor immune microenvironment. Heliyon. 2024;10(2):e23601.
- McGee LE, et al. The tumor microenvironment of metastatic osteosarcoma in the lung. Commun Biol. 2025;8:756.
- Palmerini E, et al. Tumor immune microenvironment-associated prognostic signature in osteosarcoma. Clin Cancer Res. 2025;31:3932-3943.
- Sun CY, et al. T cell exhaustion drives osteosarcoma pathogenesis. Ann Transl Med. 2021;9:1447.
- Tang H, et al. Single-cell and spatial transcriptomics reveals the key role of tip-like endothelial cells in osteosarcoma metastasis. npj Precis Oncol. 2025;9:104.
- Taylor AM, et al. Immunosuppressive tumor microenvironment of osteosarcoma. 2025. PMID: 40647416.
- Tian H, et al. Managing the immune microenvironment of osteosarcoma. Bone Res. 2023;11:11.
- van Ewijk R, et al. European standard clinical practice recommendations for children and adolescents with primary and recurrent osteosarcoma. EJC Paediatric Oncology. 2023;2:100029.
- Yang C, et al. Spatial heterogeneity of PD-1/PD-L1-defined immune context in osteosarcoma. Lab Invest. 2024;104(11):102143.
- Zhang Y, et al. CD8+ T cells, Treg balance and immune crosstalk in osteosarcoma. 2025. PMC12174160.
- Zhang Y, et al. Osteosarcoma immune microenvironment: cellular struggle and novel therapeutic insights. Front Immunol. 2025;16:1584450.