دورية أكاديمية

Prognostic impact of the post-treatment T cell composition and spatial organization in soft tissue sarcoma patients treated with neoadjuvant hyperthermic radio(chemo)therapy

التفاصيل البيبلوغرافية
العنوان: Prognostic impact of the post-treatment T cell composition and spatial organization in soft tissue sarcoma patients treated with neoadjuvant hyperthermic radio(chemo)therapy
المؤلفون: Rupp, Luise, Resag, Antonia, Potkrajcic, Vlatko, Warm, Verena, Wehner, Rebekka, Jöhrens, Korinna, Bösmüller, Hans, Eckert, Franziska, Schmitz, Marc
المساهمون: Bundesministerium für Bildung und Forschung, Deutsche Krebshilfe
المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224
بيانات النشر: Frontiers Media SA
سنة النشر: 2023
المجموعة: Frontiers (Publisher - via CrossRef)
مصطلحات موضوعية: Immunology, Immunology and Allergy
الوصف: Soft tissue sarcomas (STS) form a heterogeneous group of tumors sharing a mesenchymal origin. Despite good local control of the disease, the occurrence of distant metastases often limits survival of STS patients with localized, high-risk tumors of the extremities. Accumulating evidence suggests a central role for the tumor immune microenvironment in determining the clinical outcome and response to therapy. Thus, it has been reported that STS patients with a high immune signature and especially presence of B cells and tertiary lymphoid structures display improved overall survival and response to checkpoint inhibitor treatment. Here, we explored the effect of curative multimodal therapy on the T cell landscape of STS using multiplex immunohistochemistry. We analyzed the phenotype, frequency, and spatial distribution of STS-infiltrating CD8 + T cells by staining for CD8, 4-1BB, Granzyme B, Ki67, PD-1, and LAG-3 as well as CD3 + T helper cells using a panel consisting of CD3, T-bet, GATA3, RORγT, FoxP3, and Ki67. All patients received neoadjuvant radiotherapy plus locoregional hyperthermia with or without chemotherapy. While the treatment-naïve biopsy sample allows an analysis of baseline T cell infiltration levels, both intra- and peritumoral areas of the matched resected tissue were analyzed to assess composition and spatial distribution of the T cell compartment and its therapeutic modulation. Generally, post-treatment tissues displayed lower frequencies of CD3 + and CD8 + T cells. Association with clinical data revealed that higher post-treatment frequencies of peritumoral and intratumoral CD3 + T cells and intratumoral PD-1 + CD8 + T cells were significantly associated with improved disease-free survival (DFS), while these densities had no prognostic significance in the biopsy. Upon spatial analysis, a high ratio of intratumoral to peritumoral CD8 + T cells emerged as an independent prognostic marker for longer DFS. These results indicate that the STS T cell landscape is altered by multimodal therapy and may ...
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
DOI: 10.3389/fimmu.2023.1185197
DOI: 10.3389/fimmu.2023.1185197/full
الإتاحة: https://doi.org/10.3389/fimmu.2023.1185197Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.B109E50F
قاعدة البيانات: BASE