LAUSR

Background: Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. In contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. Materials and Methods: Plasma samples were collected prospectively from patients with advanced and metastatic renal cell carcinoma (RCC) prior to initiation of ICI treatment (baseline) and 2 or 3 weeks after the first cycle of ICI treatment (post-dose 1). Plasma cytokines and chemokines (GRO [CXCL1], IL-17A, IL-1β, IL-6, IL-8, IP-10 [CXCL10], MCP-1 [CCL2], TNFα) were measured by Luminex system, and plasma level of CXCL13 and anti-CD74 autoantibody levels were measured by ELISA. Their association with irAEs was analyzed. Results: In a discovery cohort of 13 patients, plasma levels of CXCL1, IL-17A, IL-1β, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (p=0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in a validation cohort of 43 RCC patients who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (p=0.0246 and 0.0137, respectively). We evaluated the relationship between plasma levels of CXCL10 and CXCL13, which we measured in a previous study, and the incidence of irAEs. At baseline, the plasma CXCL13 level was positively associated with the CXCL10 level (p=0.0007), but no significant association was observed post-dose 1 (p=0.2678). Plasma CXCL13 levels were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (p=0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. Conclusion: Plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs. Citation Format: Yuji Miura, Takanobu Motoshima, Toshiki Anami, Hiromu Yano, Remi Mito, Shinji Urakami, Keiichi Kinowaki, Hirotake Tsukamoto, Ryoma Kurahashi, Yoji Murakami, Junji Yatsuda, Yukio Fujiwara, Tomomi Kamba, Yoshihiro Komohara. Predictive value of CXCL10 for the occurrence of immune related adverse events in patient with renal cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4326.