@article{b52beb30a8a74eefb46a5d17a4dc1f56,
title = "The fibronectin–ILT3 interaction functions as a stromal checkpoint that suppresses myeloid cells",
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.",
author = "Paavola, {Kevin J.} and Roda, {Julie M.} and Lin, {Vicky Y.} and Peirong Chen and O{\textquoteright}Hollaren, {Kyle P.} and Richard Ventura and Crawley, {Suzanne C.} and Betty Li and Chen, {Hung I.H.} and Seth Malmersj{\"o} and Sharkov, {Nikolai A.} and Geoffrey Horner and Wei Guo and Kutach, {Alan K.} and Kalyani Mondal and Zhen Zhang and Lichtman, {Joshua S.} and Christina Song and Rivera, {Lee B.} and Wenhui Liu and Jian Luo and Yan Wang and Solloway, {Mark J.} and Allan, {Bernard B.} and Avantika Kekatpure and Starck, {Shelley R.} and Raj Haldankar and Bin Fan and Chun Chu and Jie Tang and Martina Molgora and Marco Colonna and Kaplan, {Daniel D.} and Hsu, {Jer Yuan}",
note = "Funding Information: The authors thank Lewis Lanier for providing the CT237 reporter cell line; Richard Yan for anti-ILT3 antibody production; Mehrdad Moshrefi and Keith Akama for control antibody and fibronectin production; Yiyuan Yi for hybridoma sequencing; and Raymond Li, Jing Zhou, and Jared Higbee for LAIR1-Fc production. They thank Jeong Kim, Jon Sitrin, and Geoffrey Stone for critical reading of the article and Jeong Kim and Jiping Zha for sharing unpublished data that are informative to this work. This work was supported by NGM Biopharmaceuticals. Publisher Copyright: {\textcopyright} 2021 The Authors; Published by the American Association for Cancer Research",
year = "2021",
month = nov,
doi = "10.1158/2326-6066.CIR-21-0240",
language = "English",
volume = "9",
pages = "1283--1297",
journal = "Cancer immunology research",
issn = "2326-6066",
number = "11",
}