| Autor: |
Galina Gabriely, Duanduan Ma, Shafiuddin Siddiqui, Linqing Sun, Nathaniel P. Skillin, Hadi Abou-El-Hassan, Thais G. Moreira, Dustin Donnelly, Andre P. da Cunha, Mai Fujiwara, Lena R. Walton, Amee Patel, Rajesh Krishnan, Stuart S. Levine, Brian C. Healy, Rafael M. Rezende, Gopal Murugaiyan, Howard L. Weiner |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 24, Iss 11, Pp 103347- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2021.103347 |
| Popis: |
Summary: Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-β on their surface and LAPHi MCs that stimulate Foxp3+ Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAPHi MCs. Furthermore, adoptive transfer of LAPHi MCs promotes Treg accumulation and tumor growth in vivo. Conversely, anti-LAP antibody, which reduces LAPHi MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAPHi dominated cell subsets with distinct immunosuppressive signatures, including those with high levels of MHCII and PD-L1 genes. Analogous to mice, LAP is expressed on myeloid suppressor cells in humans, and these cells are increased in glioma patients. Thus, our results identify a previously unknown function by which LAPHi MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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