Papillomavirus-associated squamous skin cancers following transplant immunosuppression: one Notch closer to control

摘要: The frequent occurrence of cutaneous squamous cell carcinomas (SCCs) containing weakly tumorigenic human papillomaviruses (HPVs) following iatrogenic immunosuppression for organ transplantation remains incompletely understood. Here we address this problem in the light recent insights into (1) association low-risk β-HPVs with skin SCCs rare genetic syndromes epidermodysplasia verruciformis and xeroderma pigmentosum, (2) recovery post-transplant tumor control on substituting calcineurin-inhibitory mTOR-inhibitory immunosuppression, (3) unexpectedly favorable prognosis node-positive high-risk α-HPVs originating activated immune niche oropharynx, (4) rapid HPV-negative ultraviolet (UV)-damaged melanoma patients receiving Raf-inhibitory drugs, (5) selective ability β-HPV E6 oncoproteins to inhibit Notch tumor-suppressive signaling mesenchymal tissues. crosstalk so implied between oncogenic UV-induced mutations, defective host immunity, β-HPV-dependent stromal-epithelial suggests that immunosuppressants such as calcineurin inhibitors intensify mitogenic signalling TP53-mutant keratinocytes while also abrogating immune-dependent Notch-mediated repression. This emerging interplay solar damage, viral homeostasis makes it timely reappraise strategies managing transplant patients.