Myeloid-targeting immunotherapies overcome inhibitory barriers in immune-evasive neuroblastoma.

ABSTRACT: Neuroblastomas are highly heterogeneous tumors originating from neural crest-derived cells destined to form the sympathetic nervous system. Nearly half of high-risk tumors present with amplification of the MYCN proto-oncogene. Here, we describe a Mycn-driven, transplantable, non-germline, genetically engineered mouse model (Mycn-nGEMM). Mycn-nGEMM tumors recapitulate the immune-evasive, macrophage-rich tumor microenvironment of high-risk, MYCN-amplified human neuroblastoma. Treatment of tumor-bearing mice with anti-PD-L1, but not anti-PD-1 or anti-CTLA-4, inhibited tumor growth, profoundly remodeling the tumor microenvironment by depleting anti-inflammatory macrophages and increasing T cell infiltration. Surprisingly, while tumor cells showed low expression of PD-L1, anti-inflammatory macr

SUBMITTER: Menard M 

PROVIDER: S-EPMC12263170 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature