Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells

Paavola, Kevin J.; Roda, Julie M.; Lin, Vicky Y.; Chen, Peirong; O'Hollaren, Kyle P.; Ventura, Richard; Crawley, Suzanne C.; Li, Betty; Chen, Hung-I H.; Malmersjö, Seth; Sharkov, Nikolai A.; Horner, Geoffrey; Guo, Wei; Kutach, Alan K.; Mondal, Kalyani; Zhang, Zhen; Lichtman, Joshua S.; Song, Christina; Rivera, Lee B.; Liu, Wenhui; Luo, Jian; Wang, Yan; Solloway, Mark J.; Allan, Bernard B.; Kekatpure, Avantika; Starck, Shelley R.; Haldankar, Raj; Fan, Bin; Chu, Chun; Tang, Jie; Molgora, Martina; Colonna, Marco; Kaplan, Daniel D.; Hsu, Jer-Yuan

doi:10.1158/2326-6066.22544375.v1

Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells

journal contribution

posted on 2023-04-04, 01:22 authored by Kevin J. Paavola, Julie M. Roda, Vicky Y. Lin, Peirong Chen, Kyle P. O'Hollaren, Richard Ventura, Suzanne C. Crawley, Betty Li, Hung-I H. Chen, Seth Malmersjö, Nikolai A. Sharkov, Geoffrey Horner, Wei Guo, Alan K. Kutach, Kalyani Mondal, Zhen Zhang, Joshua S. Lichtman, Christina Song, Lee B. Rivera, Wenhui Liu, Jian Luo, Yan Wang, Mark J. Solloway, Bernard B. Allan, Avantika Kekatpure, Shelley R. Starck, Raj Haldankar, Bin Fan, Chun Chu, Jie Tang, Martina Molgora, Marco Colonna, Daniel D. Kaplan, Jer-Yuan Hsu

Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells

Funding

NGM Biopharmaceuticals

History

ARTICLE ABSTRACT

Suppressive myeloid cells inhibit antitumor immunity by preventing T-cell responses. Immunoglobulin-like transcript 3 (ILT3; also known as LILRB4) is highly expressed on tumor-associated myeloid cells and promotes their suppressive phenotype. However, the ligand that engages ILT3 within the tumor microenvironment and renders tumor-associated myeloid cells suppressive is unknown. Using a screening approach, we identified fibronectin as a functional ligand for ILT3. The interaction of fibronectin with ILT3 polarized myeloid cells toward a suppressive state, and these effects were reversed with an ILT3-specific antibody that blocked the interaction of ILT3 with fibronectin. Furthermore, ex vivo treatment of human tumor explants with anti-ILT3 reprogrammed tumor-associated myeloid cells toward a stimulatory phenotype. Thus, the ILT3–fibronectin interaction represents a “stromal checkpoint” through which the extracellular matrix actively suppresses myeloid cells. By blocking this interaction, tumor-associated myeloid cells may acquire a stimulatory phenotype, potentially resulting in increased antitumor T-cell responses.

Usage metrics

Keywords

cancer

Licence

CC BY

Exports

RefWorks

BibTeX

Ref. manager

Endnote

DataCite

NLM

DC

Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells

Funding

NGM Biopharmaceuticals

History

ARTICLE ABSTRACT

Usage metrics

Categories

Keywords

Licence

Exports