Abstract
TREM2 is a pro-tumorigenic marker of tumor-infiltrating macrophages in mouse models and human tumors that can be targeted to curb tumor growth and improve the efficacy of checkpoint blockade therapy while remodeling the landscape of tumor-infiltrating macrophages.
Original language | English |
---|---|
Pages (from-to) | 886-900.e17 |
Journal | Cell |
Volume | 182 |
Issue number | 4 |
DOIs | |
State | Published - Aug 20 2020 |
Keywords
- TREM2
- breast cancer
- checkpoint blockade
- colorectal cancer
- human
- macrophages
- sarcoma
- tumor
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In: Cell, Vol. 182, No. 4, 20.08.2020, p. 886-900.e17.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
AU - Molgora, Martina
AU - Esaulova, Ekaterina
AU - Vermi, William
AU - Hou, Jinchao
AU - Chen, Yun
AU - Luo, Jingqin
AU - Brioschi, Simone
AU - Bugatti, Mattia
AU - Omodei, Andrea Salvatore
AU - Ricci, Biancamaria
AU - Fronick, Catrina
AU - Panda, Santosh K.
AU - Takeuchi, Yoshiko
AU - Gubin, Matthew M.
AU - Faccio, Roberta
AU - Cella, Marina
AU - Gilfillan, Susan
AU - Unanue, Emil R.
AU - Artyomov, Maxim N.
AU - Schreiber, Robert D.
AU - Colonna, Marco
N1 - Funding Information: We thank the McDonnell Genome Institute at Washington University for sequencing, Ali Ellebedy, Aaron Schmitz, Daved Fremont, and Chris Nelson for advising in the generation of the recombinant antibody, David Holtzman for supporting antibody purification, and Erica Lantelme and the Flow Cytometry Core at Washington University for sorting. We also thank Wandy Beatty, director of the Molecular Microbiology Imaging Facility at Washington University, for valuable technical support. M. Colonna was supported by the National Institutes of Health ( RF1AG05148501 and R21AG059176 ). M.M. is a recipient of the Cancer Research Institute -Lloyd J. Old Memorial Fellowship in Tumor Immunology. W.V. is supported by AIRC IG23179 . R.F. was supported by grants from the National Institutes of Health ( R01 AR066551 and R01 CA235096 ). M.M.G. was supported by a Parker Institute for Cancer Immunotherapy Bridge Scholar Award and a CPRIT Scholar in Cancer Research Grant ( RR190017 ). R.D.S. was supported by grants from the National Cancer Institute of the National Institutes of Health ( RO1CA190700 ), the Parker Institute for Cancer Immunotherapy , the Cancer Research Institute, Janssen Pharmaceutical Company of Johnson and Johnson , the Prostate Cancer Foundation , and a Stand Up to Cancer-Lustgarten Foundation Pancreatic Cancer Foundation Convergence Dream Team translational research grant. Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research . E.R.U. received support from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health ( AI114551 and DK058177 ). Funding Information: We thank the McDonnell Genome Institute at Washington University for sequencing, Ali Ellebedy, Aaron Schmitz, Daved Fremont, and Chris Nelson for advising in the generation of the recombinant antibody, David Holtzman for supporting antibody purification, and Erica Lantelme and the Flow Cytometry Core at Washington University for sorting. We also thank Wandy Beatty, director of the Molecular Microbiology Imaging Facility at Washington University, for valuable technical support. M. Colonna was supported by the National Institutes of Health (RF1AG05148501 and R21AG059176). M.M. is a recipient of the Cancer Research Institute-Lloyd J. Old Memorial Fellowship in Tumor Immunology. W.V. is supported by AIRC IG23179. R.F. was supported by grants from the National Institutes of Health (R01 AR066551 and R01 CA235096). M.M.G. was supported by a Parker Institute for Cancer Immunotherapy Bridge Scholar Award and a CPRIT Scholar in Cancer Research Grant (RR190017). R.D.S. was supported by grants from the National Cancer Institute of the National Institutes of Health (RO1CA190700), the Parker Institute for Cancer Immunotherapy, the Cancer Research Institute, Janssen Pharmaceutical Company of Johnson and Johnson, the Prostate Cancer Foundation, and a Stand Up to Cancer-Lustgarten Foundation Pancreatic Cancer Foundation Convergence Dream Team translational research grant. Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. E.R.U. received support from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (AI114551 and DK058177). M.M. W.V. S.B. M.B. and A.S.O. performed experiments and analyzed the data. B.R. S.K.P. and Y.T. performed experiments. E.E. and J.L. performed in silico analysis. C.F. performed the sequencing. J.H. Y.C. and M. Cella generated reagents. S.G. bred, maintained, and validated the Trem2?/? mouse colony. W.V. M.M.G. R.F. S.G. E.R.U. M.N.A. and R.D.S. provided expertise. M.M. M. Cella, and M. Colonna designed experiments. M.M. and M. Colonna wrote the paper with input from all authors. M. Colonna received research support from Alector, Amgen, Ono, and Pfizer for activities not related to the findings described in this publication. M. Colonna is a scientific advisory board member of Alector, Cell Signaling Technologies, and Bluefin, and has a patent to TREM2 pending. R.D.S. is a cofounder, scientific advisory board member, stockholder, and royalty recipient of Jounce Therapeutics and Neon Therapeutics and is a scientific advisory board member for A2 Biotherapeutics, BioLegend, Codiak Biosciences, Constellation Pharmaceuticals, NGM Biopharmaceuticals, and Sensei Biotherapeutics. Publisher Copyright: © 2020 Elsevier Inc.
PY - 2020/8/20
Y1 - 2020/8/20
N2 - TREM2 is a pro-tumorigenic marker of tumor-infiltrating macrophages in mouse models and human tumors that can be targeted to curb tumor growth and improve the efficacy of checkpoint blockade therapy while remodeling the landscape of tumor-infiltrating macrophages.
AB - TREM2 is a pro-tumorigenic marker of tumor-infiltrating macrophages in mouse models and human tumors that can be targeted to curb tumor growth and improve the efficacy of checkpoint blockade therapy while remodeling the landscape of tumor-infiltrating macrophages.
KW - TREM2
KW - breast cancer
KW - checkpoint blockade
KW - colorectal cancer
KW - human
KW - macrophages
KW - sarcoma
KW - tumor
UR - http://www.scopus.com/inward/record.url?scp=85089440190&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.07.013
DO - 10.1016/j.cell.2020.07.013
M3 - Article
C2 - 32783918
AN - SCOPUS:85089440190
SN - 0092-8674
VL - 182
SP - 886-900.e17
JO - Cell
JF - Cell
IS - 4
ER -