| Autor: |
Jer-Yuan Hsu, Daniel D. Kaplan, Marco Colonna, Martina Molgora, Jie Tang, Chun Chu, Bin Fan, Raj Haldankar, Shelley R. Starck, Avantika Kekatpure, Bernard B. Allan, Mark J. Solloway, Yan Wang, Jian Luo, Wenhui Liu, Lee B. Rivera, Christina Song, Joshua S. Lichtman, Zhen Zhang, Kalyani Mondal, Alan K. Kutach, Wei Guo, Geoffrey Horner, Nikolai A. Sharkov, Seth Malmersjö, Hung-I H. Chen, Betty Li, Suzanne C. Crawley, Richard Ventura, Kyle P. O'Hollaren, Peirong Chen, Vicky Y. Lin, Julie M. Roda, Kevin J. Paavola |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6550622.v1 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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