In the present study, we aim to understand the implications of transforming growth factor β1 secreted by cancer-associated fibroblasts (CAFs) in the resistance of cutaneous squamous cell carcinoma (cSCC) cells to photodynamic therapy (PDT), as well as the effects of the combination of PDT with N-acetyl cysteine (NAC). PDT is widely used for the treatment of cSCC, and it involves the combination of visible light, molecular oxygen and a photoactive compound (photosensitizer), leading to cell death owing to the generation of reactive oxygen species. TGFβ1 produced by CAFs has been implicated in cancer resistance to therapies, although its role in the resistance of cSCC to PDT has not been fully addressed yet. Related to this, NAC, a well-known treatment for pulmonary fibrosis, is known to reduce TGFβ1 levels in the tumor microenvironment. Thus, NAC in combination with PDT could improve the treatment of cSCC by counteracting the effects of CAF derived TGFβ1. To address this, we investigated the impact of CAF-derived conditioned medium on the response of cSCC cells to PDT. CAFs from patients with in situ and invasive cSCC were cultured and CAF derived conditioned medium, enriched in TGFβ1, was subsequently used to treat two established human cSCC cell lines, A431 and SCC13, before exposing them to PDT. An induction of resistance to PDT was observed in A431 but not in SCC13 cells. Data obtained from CGH-arrays and Western blot assays shed light on the molecular mechanisms behind this differential induction of resistance to PDT and, interestingly, pre-treatment of CAFs with NAC prevented this effect. Overall, our results highlight TGFβ1 as a potential target for the optimization of PDT and point to NAC as a promising adjuvant agent for the treatment of cSCC.

ESDR297 - Role of TGFβ1 in combination with N-acetyl cysteine in the response of squamous cell carcinoma to photodynamic therapy

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.