Activation of Tumor-Cell STING Primes NK-Cell Therapy
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- Erik H. Knelson
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Elena V. Ivanova
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Mubin Tarannum
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Marco Campisi
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Patrick H. Lizotte
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Matthew A. Booker
- 3Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Ismail Ozgenc
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Moataz Noureddine
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Brittany Meisenheimer
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Minyue Chen
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Brandon Piel
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Nathaniel Spicer
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Bonje Obua
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Cameron M. Messier
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Erin Shannon
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Navin R. Mahadevan
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Tetsuo Tani
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Pieter J. Schol
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Anna M. Lee-Hassett
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Ari Zlota
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Ha V. Vo
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Minh Ha
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Arrien A. Bertram
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Saemi Han
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Tran C. Thai
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Corinne E. Gustafson
- 7Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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- Kartika Venugopal
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Timothy J. Haggerty
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Thomas P. Albertson
- 7Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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- Antja-Voy Hartley
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Pinar O. Eser
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Ze-Hua Li
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Israel Cañadas
- 8Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
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- Marina Vivero
- 6Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
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- Assunta De Rienzo
- 7Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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- William G. Richards
- 7Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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- Adnan O. Abu-Yousif
- 9Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts.
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- Vicky A. Appleman
- 9Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts.
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- Richard C. Gregory
- 9Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts.
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- Alexander Parent
- 9Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts.
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- Neil Lineberry
- 9Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts.
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- Eric L. Smith
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Pasi A. Jänne
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Juan J. Miret
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Michael Y. Tolstorukov
- 3Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Rizwan Romee
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Cloud P. Paweletz
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Raphael Bueno
- 7Deparment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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- David A. Barbie
- 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Description
<jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>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.</jats:p> </jats:sec>
Journal
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- Cancer Immunology Research
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Cancer Immunology Research 10 (8), 947-961, 2022-06-02
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1360017287043540224
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- ISSN
- 23266074
- 23266066
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- Data Source
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- Crossref