Predictive value of CXCL10 for the occurrence of immune‐related adverse events in patient with renal cell carcinoma

Author:

Miura Yuji12ORCID,Motoshima Takanobu3,Anami Toshiki13,Yano Hiromu1,Mito Remi14,Pan Cheng1,Urakami Shinji5,Kinowaki Keiichi6,Tsukamoto Hirotake7,Kurahashi Ryoma3,Murakami Yoji3,Yatsuda Junji3,Fujiwara Yukio1,Kamba Tomomi3,Komohara Yoshihiro18ORCID

Affiliation:

1. Department of Cell Pathology, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan

2. Department of Medical Oncology Toranomon Hospital Tokyo Japan

3. Department of Urology, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan

4. Department of Respiratory Medicine, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan

5. Department of Urology Toranomon Hospital Tokyo Japan

6. Department of Pathology Toranomon Hospital Tokyo Japan

7. Division of Clinical Immunology and Cancer Immunotherapy, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine Kyoto University Kyoto Japan

8. Center for Metabolic Regulation of Healthy Aging Kumamoto University Kumamoto Japan

Abstract

AbstractImmune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By 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. This study investigated plasma cytokine, chemokine, and anti‐CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C–X–C motif) ligand (CXCL) 1, 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 an extended cohort of 43 patients with RCC 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). Plasma CXCL13 levels, which we measured in a previous study, 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. In 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.

Publisher

Wiley

Subject

Virology,Immunology,Microbiology

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