Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.

ABSTRACT: Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)¹. The extracellular matrix (ECM) contributes to immune exclusion². However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes^3,4. Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity⁵, instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellul

SUBMITTER: Sun X 

PROVIDER: S-EPMC8839149 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature