The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNFα.

ABSTRACT:

Unlabelled

Recently, the rationale for combining targeted therapy with immunotherapy has come to light, but our understanding of the immune response during MAPK pathway inhibitor treatment is limited. We discovered that the immune microenvironment can act as a source of resistance to MAPK pathway-targeted therapy, and moreover during treatment this source becomes reinforced. In particular, we identified macrophage-derived TNFα as a crucial melanoma growth factor that provides resistance to MAPK pathway inhibitors through the lineage transcription factor MITF (microphthalmia transcription factor). Most strikingly, in BRAF-mutant melanomas of patients and BRAF(V600E) melanoma allografts, MAPK pathway inhibitors increased the number of tumor-associated macrophages, and TNFα and MITF e

SUBMITTER: Smith MP 

PROVIDER: S-EPMC4184867 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature