Of epidermal carcinomas (EC), basal cell carcinoma (BCC) and squamous cell carcinoma (SSC) are the most common cancers worldwide. However, organ transplant recipients (OTRs) face a 10-20 fold and up to 250 fold increased risk of developing BCCs and SCCs respectively. This is thought to be due to the calcineurin inhibitor, cyclosporine (CsA), an immunosuppressant commonly prescribed to patients. Preliminary results showed CsA to increase the size and number of BCC lesions, particularly near hair follicles (HF). UV radiation is also a common carcinogen for skin cancer. Thus, the study aimed to evaluate epidermal clone size dynamics and proliferation of keratinocytes in CsA-treated skin and the synergy between CsA and UV. A multilineage tracing model K14Cre x craggsbowwt/+, (Skinbow) allowed us to analyse the epidermal clone dynamic according to their size.
In young mice, CsA showed to increase clone size and a minor increase in proliferation. However, this was not comparable to the effects of UV radiation which greatly increased clone size and proliferation in both young and old mice. There were no synergistic effects between CsA and UV. Of note, the findings here support the hypothesis that HFs may have a role in skin cancer development.
This study suggests that CsA, with its immunosuppressive capabilities, complements the mutagenic effect of UV radiation for cancer development. It also provides a strong foundation for additional studies, such as additional investigations on the long-term effects of CsA.