Nonclinical in-vitro evaluation of the transcriptomic and metabolic effects of immune checkpoint inhibitors on sunitinib-resistant renal cell carcinoma

Recently, immune checkpoint inhibitors (ICIs) have been approved as first line and second-line therapies for individuals with advanced renal cell carcinoma (RCC) who developed a resistance to anti-angiogenic therapies. It remains unknown how ICIs efficacy is affected by the development of resistance to anti-angiogenic inhibitors. Thus, our goal is to evaluate transcriptomic and metabolic effects after ICI therapy of sunitinib-resistant RCC and compare the efficacy of ICIs between naïve and sunitinib-resistant RCC. Two Sunitinib-resistant human advanced renal cell carcinoma cell lines A498-Su and 786-O Su were developed from parental A498 and 786-O, respectively. Sunitinib resistant cells were then treated separately with three ICIs like Atezolizumab (At), Avelumab (Av), and Durvalumab (Dur) with a concentration of 10mg/mL for 24 hours and undergone in vitro metabolomics and transcriptomics analyses to investigate metabolic and transcriptomic rewiring, if any.