RCCSeq: uncovering predictive biomarkers of immunotherapy outcomes for elderly patients with metastasized renal cell carcinoma using PBMC multimodal single-cell analysis

• Applicant: Dr. Charis Kalogirou
• Subject Area: Reproductive Medicine, Urology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511993132

Background:The introduction of PD-L1/CTLA-4-based immune checkpoint inhibitor (IO) therapies in oncology has revolutionised the treatment landscape of metastatic renal cell carcinoma(mRCC). Although patients now benefit from significantly improved survival rates, important clinical problems remain unanswered: for example, valid prognostic markers regarding therapy response or the development of (potentially life-threatening) therapy-associated adverse effects are not yet available. This is particularly important for older patients: not only does the response to IO therapy decrease with increasing age, but also a frequently increasing comorbidity profile makes this patient group particularly vulnerable with regard to the development of severe immune-associated side effects. Project design:The project presented here aims to answer these clinical questions as follows: on the one hand, single-cell RNA sequencing of immune cells of the peripheral blood of older and younger mRCC will be performed before and during IO therapy. At the same time, archived primary tumour material will be examined using multiplex immunofluorescence to better understand the immunological tumour microenvironment of each respective patient. The clinical endpoints of the study are primary therapy response as well as the development of severe therapy-associated side effects. Outlook:This project aims to identify non-invasive biomarkers with the methods outlined above that can significantly improve future therapy planning for mRCC patients of all ages.

• DFG Programme: Research Grants
• Co-Investigators: Clement Cochain, Ph.D.; Dr. Mathias Rosenfeldt; Professor Dr. Antoine-Emmanuel Saliba