Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis.

ABSTRACT: Age is a significant risk factor for the development of cancer. However, the mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop a mouse model that mimics the aged skin microenvironment. Using this model, here we find that senescent stromal cells are sufficient to drive localized increases in suppressive myeloid cells that contributed to tumour promotion. Further, we find that the stromal-derived senescence-associated secretory phenotype factor interleukin-6 orchestrates both increases in suppressive myeloid cells and their ability to inhibit anti-tumour T-cell responses. Significantly, in aged, cancer-free individuals, we find similar increases in immune cells that also localize near se

SUBMITTER: Ruhland MK 

PROVIDER: S-EPMC4899869 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature