Back to Search
Start Over
MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression
- Source :
- Oncoimmunology, article-version (VoR) Version of Record, OncoImmunology, Vol 11, Iss 1 (2022)
- Publication Year :
- 2022
- Publisher :
- Informa UK Limited, 2022.
-
Abstract
- The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation of immune tolerance mechanisms in the osteosarcoma microenvironment and a new therapeutic strategy. Clearance of apoptotic cells by phagocytes, a process termed “efferocytosis,” is ubiquitous in tumors and mediates the suppression of innate immune inflammatory response. Considering the massive infiltrated macrophages in osteosarcoma, efferocytosis probably serves as a potential target, but is rarely studied in osteosarcoma. Here, we verified M2 polarization and PD-L1 expression of macrophages following efferocytosis. Pharmacological inhibition and genetic knockdown were used to explore the underlying pathway. Moreover, tumor progression and immune landscape were evaluated following inhibition of efferocytosis in osteosarcoma model. Our study indicated that efferocytosis promoted PD-L1 expression and M2 polarization of macrophages. Ëfferocytosis was mediated by MerTK receptor in osteosarcoma and regulated the phenotypes of macrophages through the p38/STAT3 pathway. By establishing the murine osteosarcoma model, we emphasized that inhibition of MerTK suppressed tumor growth and enhanced the T cell cytotoxic function by increasing the infiltration of CD8+ T cells and decreasing their exhaustion. Our findings demonstrate that MerTK-mediated efferocytosis promotes osteosarcoma progression by enhancing M2 polarization of macrophages and PD-L1-induced immune tolerance, which were regulated through the p38/STAT3 pathway.
- Subjects :
- musculoskeletal diseases
Efferocytosis
PD-L1
immune tolerance
Osteosarcoma
c-Mer Tyrosine Kinase
M2 polarization
Immunology
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Bone Neoplasms
RC581-607
CD8-Positive T-Lymphocytes
B7-H1 Antigen
Mice
MerTK
Oncology
Tumor Microenvironment
Animals
Humans
Immunology and Allergy
Immunologic diseases. Allergy
RC254-282
Research Article
Subjects
Details
- ISSN :
- 2162402X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- OncoImmunology
- Accession number :
- edsair.doi.dedup.....e3d5587beb2b41356a3ccb3a79fe27c9