Theme Understanding the impact of complement dysregulation in immunosuppressive microenvironments


Title Lecture: Understanding the impact of complement dysregulation in immunosuppressive microenvironments

Keynote speaker: Monica Olcina, Group Leader in the department of Oncology, University of Oxford and an Associate Research Fellow at St Hilda’s College and Course Director of the MSc in Radiation Biology

Monica studied Pharmacy at the University of Manchester. After completing the required training to become a registered pharmacist she moved to Oxford to undertake her Masters and DPhil studies in Radiation Biology. In 2014, she joined Stanford University where she worked as a Cancer Research Institute Irvington Postdoctoral Fellow to identify novel pathways that could be targeted to improve radiotherapy. During this time, she identified the complement system as an important player in regulating both tumour and normal tissue responses to irradiation. In 2019 she moved to the University of Zurich to continue these studies. In December 2020 she returned to Oxford where she currently heads a group focused on understanding the causes and consequences of complement system dysregulation in the tumour microenvironment.

As part of this work, the Olcina group has focused on understanding the regulation of complement system proteins in tumour models characterised by highly immunosuppressive features. This work has found that in tumour models with high stromal infiltration and low CD8+ T cell numbers, the complement system is the first immune system pathway to be upregulated following radiotherapy. This includes upregulation of complement receptor C5aR1 in the epithelial compartment of these tumours. While the main proinflammatory functions of complement receptor C5aR1 are well characterised, we are beginning to uncover autocrine roles for C5aR1 in regulating cell fate following stresses induced following cancer treatment. This is important since it suggests that therapeutically targeting C5aR1 could be beneficial for treatment outcome. Our work indeed suggests that C5aR1 antagonism improves radiotherapy response even in those tumours displaying immunosuppressive features. Mechanistically, we think this occurs, at least in part, due to increased radiotherapy-induced cell death occurring because of reduced pro-survival signalling (downstream of C5aR1 inhibition). We are continuing this work to understand whether C5aR1 or other members of the complement system could be targeted to improve cancer treatments and/or whether measuring plasma levels of complement components can serve as markers of treatment response.

Host: Iosifina Foskolou

Date and Location

Time From 01:00 pm to 02:00 pm
Duration 1 hour
Start date Tuesday, May 9, 2023
Location Sanquin Auditorium (Plesmanlaan 125, Amsterdam) or on-line.