TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

Martina Molgora; Ekaterina Esaulova; William Vermi; Jinchao Hou; Yun Chen; Jingqin Luo; Simone Brioschi; Mattia Bugatti; Andrea Salvatore Omodei; Biancamaria Ricci; Catrina Fronick; Santosh K. Panda; Yoshiko Takeuchi; Matthew M. Gubin; Roberta Faccio; Marina Cella; Susan Gilfillan; Emil R. Unanue; Maxim N. Artyomov; Robert D. Schreiber; Marco Colonna

doi:10.1016/j.cell.2020.07.013

TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

Martina Molgora, Ekaterina Esaulova, William Vermi, Jinchao Hou, Yun Chen, Jingqin Luo, Simone Brioschi, Mattia Bugatti, Andrea Salvatore Omodei, Biancamaria Ricci, Catrina Fronick, Santosh K. Panda, Yoshiko Takeuchi, Matthew M. Gubin, Roberta Faccio, Marina Cella, Susan Gilfillan, Emil R. Unanue, Maxim N. Artyomov, Robert D. SchreiberMarco Colonna

Research output: Contribution to journal › Article › peer-review

215 Scopus citations

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	https://doi.org/10.1016/j.cell.2020.07.013
State	Published - Aug 20 2020

Keywords

TREM2
breast cancer
checkpoint blockade
colorectal cancer
human
macrophages
sarcoma
tumor

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10.1016/j.cell.2020.07.013

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Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., Fronick, C., Panda, S. K., Takeuchi, Y., Gubin, M. M., Faccio, R., Cella, M., Gilfillan, S., Unanue, E. R., Artyomov, M. N., ... Colonna, M. (2020). TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy. Cell, 182(4), 886-900.e17. https://doi.org/10.1016/j.cell.2020.07.013

@article{17fc51faa82e4916bf63cecf4eb3c4d1,

title = "TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy",

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.",

keywords = "TREM2, breast cancer, checkpoint blockade, colorectal cancer, human, macrophages, sarcoma, tumor",

author = "Martina Molgora and Ekaterina Esaulova and William Vermi and Jinchao Hou and Yun Chen and Jingqin Luo and Simone Brioschi and Mattia Bugatti and Omodei, {Andrea Salvatore} and Biancamaria Ricci and Catrina Fronick and Panda, {Santosh K.} and Yoshiko Takeuchi and Gubin, {Matthew M.} and Roberta Faccio and Marina Cella and Susan Gilfillan and Unanue, {Emil R.} and Artyomov, {Maxim N.} and Schreiber, {Robert D.} and Marco Colonna",

note = "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: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = aug,

day = "20",

doi = "10.1016/j.cell.2020.07.013",

language = "English",

volume = "182",

pages = "886--900.e17",

journal = "Cell",

issn = "0092-8674",

number = "4",

}

Molgora, M, Esaulova, E, Vermi, W, Hou, J, Chen, Y, Luo, J , Brioschi, S, Bugatti, M, Omodei, AS, Ricci, B, Fronick, C, Panda, SK, Takeuchi, Y, Gubin, MM, Faccio, R , Cella, M , Gilfillan, S, Unanue, ER, Artyomov, MN , Schreiber, RD & Colonna, M 2020, 'TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy', Cell, vol. 182, no. 4, pp. 886-900.e17. https://doi.org/10.1016/j.cell.2020.07.013

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 -

TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

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Keywords

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