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Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.
Goff, Peter H; Riolobos, Laura; LaFleur, Bonnie J; Spraker, Matthew B; Seo, Y David; Smythe, Kimberly S; Campbell, Jean S; Pierce, Robert H; Zhang, Yuzheng; He, Qianchuan; Kim, Edward Y; Schaub, Stephanie K; Kane, Gabrielle M; Mantilla, Jose G; Chen, Eleanor Y; Ricciotti, Robert; Thompson, Matthew J; Cranmer, Lee D; Wagner, Michael J; Loggers, Elizabeth T; Jones, Robin L; Murphy, Erin; Blumenschein, Wendy M; McClanahan, Terrill K; Earls, Jon; Flanagan, Kevin C; LaFranzo, Natalie A; Kim, Teresa S; Pollack, Seth M.
Afiliación
  • Goff PH; Department of Radiation Oncology, University of Washington Medicine, Seattle, Washington.
  • Riolobos L; Department of Medicine, University of Washington Medicine, Seattle, Washington.
  • LaFleur BJ; Department of Cancer Vaccine Institute, University of Washington Medicine, Seattle, Washington.
  • Spraker MB; University of Arizona BIO5 Institute, Tucson, Arizona.
  • Seo YD; Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
  • Smythe KS; Department of Surgery, University of Washington Medicine, Seattle, Washington.
  • Campbell JS; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Pierce RH; Sensei Biotherapeutics, Inc., Boston, Massachusetts.
  • Zhang Y; Sensei Biotherapeutics, Inc., Boston, Massachusetts.
  • He Q; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Kim EY; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Schaub SK; Department of Radiation Oncology, University of Washington Medicine, Seattle, Washington.
  • Kane GM; Department of Radiation Oncology, University of Washington Medicine, Seattle, Washington.
  • Mantilla JG; Department of Radiation Oncology, University of Washington Medicine, Seattle, Washington.
  • Chen EY; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
  • Ricciotti R; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
  • Thompson MJ; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
  • Cranmer LD; Department of Orthopedics and Sports Medicine, University of Washington, Seattle, Washington.
  • Wagner MJ; Seattle Cancer Care Alliance, Seattle, Washington.
  • Loggers ET; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Jones RL; Seattle Cancer Care Alliance, Seattle, Washington.
  • Murphy E; Department of Medical Oncology, University of Washington Medicine, Seattle, Washington.
  • Blumenschein WM; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • McClanahan TK; Seattle Cancer Care Alliance, Seattle, Washington.
  • Earls J; Department of Medical Oncology, University of Washington Medicine, Seattle, Washington.
  • Flanagan KC; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • LaFranzo NA; Seattle Cancer Care Alliance, Seattle, Washington.
  • Kim TS; Department of Medical Oncology, University of Washington Medicine, Seattle, Washington.
  • Pollack SM; Sarcoma, Royal Marsden Hospital NHS Trust/Institute of Cancer Research, London, United Kingdom.
Clin Cancer Res ; 28(8): 1701-1711, 2022 04 14.
Article en En | MEDLINE | ID: mdl-35115306
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias de los Tejidos Blandos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias de los Tejidos Blandos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos