Psoriasis-like disease prevents squamous skin tumor development by neutrophil-driven inflammation

Although growing evidence links chronic inflammation with increased cancer risk, the association between psoriasis and cutaneous squamous cell carcinoma (cSCC) is still elusive. Using cell transplantation and chemical-induced models of cSCC combined with inducible genetically engineered mouse models (GEMMs) of psoriasis, we investigated how chronic skin and systemic inflammation affects squamous skin tumor initiation and progression.

Here we show that in the context of severe psoriasis-like disease, neutrophil-dependent inflammation prevents squamous skin tumor development. Cellular and molecular analyses of psoriasis-like skin at the tumor initiation stage revealed a marked infiltration of CD54–expressing neutrophils, associated with the release of cytotoxic granules and neutrophil extracellular traps (NETs), as well as enhanced senescence and the expression of senescence-associated secretory phenotype (SASP) in keratinocytes.