Väitös (iho- ja sukupuolitautioppi): MD Pegah Rahmati Nezhad

MD Pegah Rahmati Nezhad esittää väitöskirjansa ”The Role of Complement Factors D and I in Cutaneous Squamous Cell Carcinoma” julkisesti tarkastettavaksi Turun yliopistossa lauantaina 30.9.2023 klo 12.00 (Turun yliopisto, Osmo Järvi -sali, Medisiina C, Kiinamyllynkatu 10, Turku).

Vastaväittäjänä toimii dosentti Hanna Jarva (Helsingin yliopisto) ja kustoksena dosentti Liisa Nissinen (Turun yliopisto). Tilaisuus on englanninkielinen. Väitöksen alana on iho- ja sukupuolitautioppi.

Väitöskirja yliopiston julkaisuarkistossa: https://urn.fi/URN:ISBN:978-951-29-9428-1


Tiivistelmä väitöstutkimuksesta:

The most common metastatic skin cancer is squamous cell carcinoma (SCC) of the skin, the incidence of which is growing worldwide. Metastatic skin SCC causes 20% of skin cancer deaths. According to the Finnish Cancer Registry, the incidence of skin SCC ranks fifth in men and sixth in women among the most common cancers in Finland.

The complement system is the backbone of natural immunity, and is considered as a double-edged sword in the tumor field; although it is known that systemic complement activation induces an anti-cancer immune response, local production and activation of complement can promote cancer development. Complement components are present in the tumor microenvironment, and research has disclosed that tumor cells are able of generating a great spectrum of complement components on site.

In this study, elevated levels of complement factor D (FD) were revealed in human skin SCC cells vs. normal surface cells of the skin (keratinocytes) in culture. The production of FD was shown to be stronger in human skin SCC tissue than in SCC precursor tissue. Also, targeted inhibition of FD production by a drug called danicopan suppressed proliferation of cultured SCC cells of the skin. It was disclosed that blocking the production of complement factor I (FI) in skin SCC cells in culture reduces their spread, and inversely inducing the overexpression of FI enhances the proliferation and spread of cancer cells. Aside from investigating the role of FD and FI in skin SCC, all complement-targeted drugs under clinical and preclinical trials were thoroughly reviewed in this thesis.

The discoveries of this dissertation indicate that FD and FI can be potentially used as novel promising markers of invasive SCC of the skin to improve precision diagnosis, classification, prognostication and therapy of this cancer. Besides, for the first time in science, the FD inhibitor drug danicopan is proposed as a highly specific and sensitive medicine for precision treatment of skin SCC.