NGFR induces melanoma invasion and immunotherapy resistance through myosin light chain 2 modulation

ABSTRACT: Immunotherapy has reshaped melanoma treatment, yet the majority of patients fail to respond or develop resistance. Nerve growth factor receptor (NGFR/p75NTR/CD271) has been linked to melanoma aggressiveness and therapeutic resistance, but the underlying mechanisms remain unclear. Here, we demonstrate that pharmacologic inhibition of NGFR with THX B significantly reduces distant metastasis and restores sensitivity in immunotherapy resistant tumors. THX B treatment also enhances intratumoral CD8⁺ T cell infiltration. Further, we show that immune resistant melanomas acquire an invasive, amoeboid phenotype characterized by elevated NGFR, PD L1, and activation of non muscle myosin light chain 2 (NM II; MLC2). Mechanistically, NGFR regulates RhoA/ROCK-dependent MLC2 phosphorylation and proteasom

SUBMITTER: Laura Nogués 

PROVIDER: S-SCDT-10_1038-S44318-026-00803-2 | biostudies-other |

REPOSITORIES: biostudies-other