Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy.

ABSTRACT: Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34⁺ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγ^null (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3⁺ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8⁺/Granz B⁺ T cells homeostasis are obs

SUBMITTER: Somasundaram R 

PROVIDER: S-EPMC7804257 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature