دورية أكاديمية
Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.
| العنوان: | Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. |
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| المؤلفون: | Goff, PH, Riolobos, L, LaFleur, BJ, Spraker, MB, Seo, YD, Smythe, KS, Campbell, JS, Pierce, RH, Zhang, Y, He, Q, Kim, EY, Schaub, SK, Kane, GM, Mantilla, JG, Chen, EY, Ricciotti, R, Thompson, MJ, Cranmer, LD, Wagner, MJ, Loggers, ET, Jones, RL, Murphy, E, Blumenschein, WM, McClanahan, TK, Earls, J, Flanagan, KC, LaFranzo, NA, Kim, TS, Pollack, SM |
| المساهمون: | Jones, Robin |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Humans, Sarcoma, Soft Tissue Neoplasms, Prognosis, Neoadjuvant Therapy, Retrospective Studies, Immunity, Tumor Microenvironment |
| الوصف: | Purpose To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design. Experimental design Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis. Results All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy. The most prevalent immune cells in the tumor before neoadjuvant therapy were myeloid cells (45% of all immune cells) and B cells (37%), with T (13%) and natural killer (NK) cells (5%) also present. Neoadjuvant therapy significantly increased the total immune cells infiltrating the tumors across all histologic subtypes for patients receiving neoadjuvant radiotherapy with or without chemotherapy. An increase in the percentage of monocytes and macrophages, particularly M2 macrophages, B cells, and CD4+ T cells was observed postneoadjuvant therapy. Upregulation of genes and cytokines associated with antigen presentation was also observed, and a favorable pathologic response (≥90% necrosis postneoadjuvant therapy) was associated with an increase in monocytic infiltrate. Upregulation of the T-cell checkpoint TIM3 and downregulation of OX40 were observed posttreatment. Conclusions Standard neoadjuvant therapy induces both immunostimulatory and immunosuppressive effects within a complex sarcoma microenvironment dominated by myeloid and B cells. This work informs ongoing efforts to incorporate immune checkpoint inhibitors and novel immunotherapies into the neoadjuvant setting for STSs. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; 1711; application/pdf |
| اللغة: | English |
| تدمد: | 1078-0432 1557-3265 |
| العلاقة: | Clinical cancer research : an official journal of the American Association for Cancer Research, 2022, 28 (8), pp. 1701 - 1711; https://repository.icr.ac.uk/handle/internal/5098Test |
| DOI: | 10.1158/1078-0432.ccr-21-4239 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.ccr-21-4239Test https://repository.icr.ac.uk/handle/internal/5098Test |
| حقوق: | http://www.rioxx.net/licenses/all-rights-reservedTest |
| رقم الانضمام: | edsbas.E43FFD44 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10780432 15573265 |
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| DOI: | 10.1158/1078-0432.ccr-21-4239 |