RCCSeq: uncovering predictive biomarkers of immunotherapy outcomes for elderly patients with metastasized renal cell carcinoma using PBMC multimodal single-cell analysis
Final Report Abstract
The introduction of immune checkpoint inhibitor therapies in oncology (IO) has revolutionized the treatment landscape of metastatic renal cell carcinoma (mRCC). Although patients benefit from significantly improved survival rates, important questions remain unanswered: to date, neither validated prognostic markers for predicting the response to immunotherapy nor for the development of therapy-associated adverse effects are available. This issue is particularly relevant for older patients: not only does the response to IO therapy decrease with age, but an often-increasing comorbidity profile makes this patient group particularly vulnerable to the development of severe immune-related adverse effects. The present project addressed the aforementioned clinical questions as follows: Single-cell RNA sequencing of immune cells from peripheral blood was performed on both older and younger mRCC patients before and during IO therapy to identify potential prognostic factors related to treatment response and adverse effect profiles. The results showed that single-cell sequencing of peripheral immune cells was not suitable for predicting therapy response or the development of adverse effects in the context of aging. However, a subsequent spatial transcriptomics analysis of the patients' primary tumors and metastases demonstrated that a high immune cell infiltration of metastases—but not of primary tumors—was prognostic for therapy response. We aim to validate these findings in further studies.
