Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

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RESEARCH PRODUCT

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Ornella Urzì Alice Conigliaro Marco Pio La Manna Riccardo Alessandro Nadia Caccamo Maria Antonietta Di Bella Marzia Pucci Stefania Raimondo Marta Moschetti Simona Fontana

subject

STAT3 Transcription Factor PD-L1 QH301-705.5 colorectal cancer small extracellular vesicles B7-H1 Antigen Article Catalysis Stat3 Signaling Pathway Proinflammatory cytokine M0 macrophage Inorganic Chemistry Extracellular Vesicles Settore BIO/13 - Biologia Applicata Cell Line Tumor PD-L1 Tumor-Associated Macrophages small extracellular vesicle Humans Macrophage TLR4 Biology (General)Physical and Theoretical Chemistry M0 macrophages QD1-999 Molecular Biology Spectroscopy Inflammation Tumor microenvironment biology Interleukin-6 Chemistry Organic Chemistry General Medicine Computer Science Applications Gene Expression Regulation Neoplastic Toll-Like Receptor 4 multiple myeloma Chemistry Cell culture Tumor progression Colonic Neoplasms biology.protein Cancer research TLR4 Signal Transduction

description

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.

year	journal	country	edition	language
2021-11-09	International Journal of Molecular Sciences

https://doi.org/10.3390/ijms222212118