The usefulness of meflin expression in cancer-associated fibroblasts as a predictive marker for immune checkpoint inhibitor in clear cell renal cell carcinoma.

Abstract

699 Background: Tumor is composed of various cells, including not only cancer cells, but also immune cells, vascular endothelial cells and cancer associated fibroblasts (CAFs). CAFs generally work to promote cancer malignancy by secreting growth factors, promoting angiogenesis and producing extra cellular matrix. However, depletion of these CAFs accelerated tumor progression. Therefore, it is a common belief that there are two kinds of CAFs, cancer-promoting CAFs and cancer-restraining CAFs. Recently, our research group identified cancer-restraining CAFs expressing Meflin as a marker in pancreatic cancer. Furthermore, our research group reported that Meflin can be a good predictive marker for ICI in non-small cell lung cancer. This time, we performed a similar analysis for clear cell renal cell carcinoma (ccRCC), to confirm whether Meflin is universally a good predictive marker for ICI or not. Methods: This analysis was performed as a retrospective observational study and conducted in accordance with the Helsinki Declaration for Human Research and approved by the Ethics Committee of Nagoya University Graduate School of Medicine (approval number: 2020-0321).We identified 21 eligible patients with ccRCC who received ICI from 2017 to Mar 2019. We collected FFPE tissue and prepared 4–µm-thick slides for the analysis of Meflin expression by RNA in-situ hybridization (ISH). Then, we assessed the number of Meflin-positive CAFs and divided the patients into Meflin-high (15% and more CAFs express Meflin) and -Low groups, followed by the evaluation of the clinical outcomes, objective response rate (ORR) and overall survival (OS). Results: Patients were followed-up until the Aug 2022. 13 patients were divided into Meflin-high and 8 patients were divided into Meflin-low groups. Analysis revealed that 9 (69.23%) of 13 Meflin-high patients responded to ICI. In contrast, none (0%) of 8 Meflin-low patients showed any significant response (p-value: 0.0046). Furthermore, Kaplan–Meier survival analysis revealed, the Meflin-high group had a significantly favorable prognosis in OS (p-value:0.0137, hazard ratio 0.2959[0.06933 to 0.7097]). Conclusions: This analysis concluded that Meflin is a good predictive biomarker for ICI in ccRCC.