Nature Communications (Jul 2022)
HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors
- Lei Guan,
- Bin Wu,
- Ting Li,
- Lynn A. Beer,
- Gaurav Sharma,
- Mingyue Li,
- Chin Nien Lee,
- Shujing Liu,
- Changsong Yang,
- Lili Huang,
- Dennie T. Frederick,
- Genevieve M. Boland,
- Guangcan Shao,
- Tatyana M. Svitkina,
- Kathy Q. Cai,
- Fangping Chen,
- Meng-Qiu Dong,
- Gordon B. Mills,
- Lynn M. Schuchter,
- Giorgos C. Karakousis,
- Tara C. Mitchell,
- Keith T. Flaherty,
- David W. Speicher,
- Youhai H. Chen,
- Meenhard Herlyn,
- Ravi K. Amaravadi,
- Xiaowei Xu,
- Wei Guo
Affiliations
- Lei Guan
- Department of Biology, School of Arts & Sciences, University of Pennsylvania
- Bin Wu
- Department of Biology, School of Arts & Sciences, University of Pennsylvania
- Ting Li
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Lynn A. Beer
- Molecular & Cellular Oncogenesis Program, Wistar Institute
- Gaurav Sharma
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
- Mingyue Li
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Chin Nien Lee
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Shujing Liu
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Changsong Yang
- Department of Biology, School of Arts & Sciences, University of Pennsylvania
- Lili Huang
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Dennie T. Frederick
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School
- Genevieve M. Boland
- Department of Surgical Oncology, Massachusetts General Hospital
- Guangcan Shao
- National Institute of Biological Sciences
- Tatyana M. Svitkina
- Department of Biology, School of Arts & Sciences, University of Pennsylvania
- Kathy Q. Cai
- Histopathology Facility, Fox Chase Cancer Center
- Fangping Chen
- Histotechnology Facility, The Wistar Institute
- Meng-Qiu Dong
- National Institute of Biological Sciences
- Gordon B. Mills
- Division of Oncological Science, School of Medicine and Knight Cancer Institute, Oregon Health & Science University
- Lynn M. Schuchter
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
- Giorgos C. Karakousis
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Tara C. Mitchell
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
- Keith T. Flaherty
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School
- David W. Speicher
- Molecular & Cellular Oncogenesis Program, Wistar Institute
- Youhai H. Chen
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Meenhard Herlyn
- Molecular & Cellular Oncogenesis Program, Wistar Institute
- Ravi K. Amaravadi
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
- Xiaowei Xu
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Wei Guo
- Department of Biology, School of Arts & Sciences, University of Pennsylvania
- DOI
- https://doi.org/10.1038/s41467-022-31713-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 12
Abstract
Lack of CD8+ T-cell infiltration into solid tumors is associated with poor responsiveness to immune checkpoint therapy (ICT). Here, the authors show that blocking the phosphorylation of HRS to reduce the induction of immunosuppressive exosomes promotes CD8+ T-cell infiltration into tumors and enhances the efficacy of ICT in mouse melanoma models.
