github link
Accession IconGSE49632

TLR2/6 agonists and IFNlambda induce CXCL10 from melanoma

Organism Icon Homo sapiens
Sample Icon 56 Downloadable Samples
Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Submitter Supplied Information

Description
Melanoma is the most lethal form of skin cancer. Clinical efforts to combat melanoma include immune therapies whose benefit depends on antitumor T-cells, to target and to clear melanoma. However, most tumors lack significant immune infiltration prior to therapy, and some immune therapies are hindered by a persistent lack of immune-cell infiltration. Chemokines can promote T-cell migration into tumors; therefore, agents that induce T-cell attracting chemokines in the tumor microenvironment could potentially improve the clinical activity of current immune therapies for melanoma. CXCL10 has been implicated as a critical chemokine supporting T-cell infiltration into the tumor microenvironment. Here we report that combination treatment of human melanoma cell lines with Toll-like receptor (TLR) 2/6 agonists MALP-2 or FSL-1 +IFNlambda synergize to induce production of immune-cell attracting chemokines CCL3 and CXCL10 by melanoma cells. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that stimulation of fresh patient melanoma specimens with TLR2/6 agonists+IFNlambda induces CXCL10 production from melanoma cells, endothelial and immune-cells. Furthermore, ex vivo migration assays demonstrate that stimulation of melanoma cells with TLR2/6 agonists+IFNlambda increases CD4+ and CD8+ T-cell migration toward melanoma. Collectively, these data identify a novel synergy of TLR2/6 agonists+IFNlambda for inducing CXCL10 production by melanoma cells and suggest that intralesional administration of TLR2/6 agonists+IFNlambda may improve immune signatures in melanoma metastases and have value in combination with other immune therapies, by supporting better T-cell migration to melanoma.
PubMed ID
No associated PubMed ID
Publication Title
No associated publication
Total Samples
56
Submitter’s Institution
Authors
No associated authors

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Disease
Disease stage
Cell line
Processing Information
Additional Metadata
No rows found
Loading...