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Activation of Tumor-Cell STING Primes NK-Cell Therapy.
Knelson, Erik H; Ivanova, Elena V; Tarannum, Mubin; Campisi, Marco; Lizotte, Patrick H; Booker, Matthew A; Ozgenc, Ismail; Noureddine, Moataz; Meisenheimer, Brittany; Chen, Minyue; Piel, Brandon; Spicer, Nathaniel; Obua, Bonje; Messier, Cameron M; Shannon, Erin; Mahadevan, Navin R; Tani, Tetsuo; Schol, Pieter J; Lee-Hassett, Anna M; Zlota, Ari; Vo, Ha V; Ha, Minh; Bertram, Arrien A; Han, Saemi; Thai, Tran C; Gustafson, Corinne E; Venugopal, Kartika; Haggerty, Timothy J; Albertson, Thomas P; Hartley, Antja-Voy; Eser, Pinar O; Li, Ze-Hua; Cañadas, Israel; Vivero, Marina; De Rienzo, Assunta; Richards, William G; Abu-Yousif, Adnan O; Appleman, Vicky A; Gregory, Richard C; Parent, Alexander; Lineberry, Neil; Smith, Eric L; Jänne, Pasi A; Miret, Juan J; Tolstorukov, Michael Y; Romee, Rizwan; Paweletz, Cloud P; Bueno, Raphael; Barbie, David A.
Afiliação
  • Knelson EH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Ivanova EV; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Tarannum M; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Campisi M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Lizotte PH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Booker MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Ozgenc I; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Noureddine M; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Meisenheimer B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Chen M; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Piel B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Spicer N; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Obua B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Messier CM; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Shannon E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Mahadevan NR; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
  • Tani T; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Schol PJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Lee-Hassett AM; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Zlota A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Vo HV; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Ha M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Bertram AA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Han S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Thai TC; Graduate Medical Sciences Program, Boston University School of Medicine, Boston, Massachusetts.
  • Gustafson CE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Venugopal K; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
  • Haggerty TJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Albertson TP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Hartley AV; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Eser PO; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Li ZH; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Cañadas I; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Vivero M; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • De Rienzo A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Richards WG; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Abu-Yousif AO; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Appleman VA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Gregory RC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Parent A; Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
  • Lineberry N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Smith EL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Jänne PA; Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
  • Miret JJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Tolstorukov MY; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Romee R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Paweletz CP; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Bueno R; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
  • Barbie DA; Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Cancer Immunol Res ; 10(8): 947-961, 2022 08 03.
Article em En | MEDLINE | ID: mdl-35678717
Activation of the stimulator of interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding of the mechanism of action of STING agonists in human tumors is key to developing therapeutic combinations that activate effective innate antitumor immunity. Here, we report that malignant pleural mesothelioma cells robustly express STING and are responsive to STING agonist treatment ex vivo. Using dynamic single-cell RNA sequencing of explants treated with a STING agonist, we observed CXCR3 chemokine activation primarily in tumor cells and cancer-associated fibroblasts, as well as T-cell cytotoxicity. In contrast, primary natural killer (NK) cells resisted STING agonist-induced cytotoxicity. STING agonists enhanced migration and killing of NK cells and mesothelin-targeted chimeric antigen receptor (CAR)-NK cells, improving therapeutic activity in patient-derived organotypic tumor spheroids. These studies reveal the fundamental importance of using human tumor samples to assess innate and cellular immune therapies. By functionally profiling mesothelioma tumor explants with elevated STING expression in tumor cells, we uncovered distinct consequences of STING agonist treatment in humans that support testing combining STING agonists with NK and CAR-NK cell therapies.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Imunoterapia Adotiva / Mesotelioma Maligno / Proteínas de Membrana Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Imunoterapia Adotiva / Mesotelioma Maligno / Proteínas de Membrana Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article