Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

// Taku Fujimura 1 , Yota Sato 1 , Kayo Tanita 1 , Yumi Kambayashi 1 , Atsushi Otsuka 2 , Yasuhiro Fujisawa 3 , Koji Yoshino 4 , Shigeto Matsushita 5 , Takeru Funakoshi 6 , Hiroo Hata 7 , Yuki Yamamoto 8 , Hiroshi Uchi 9 , Yumi Nonomura 2 , Ryota Tanaka 3 , Megumi Aoki 5 , Keisuke Imafuku 7 , Hisako Okuhira 8 , Sadanori Furudate 1 , Takanori Hidaka 1 and Setsuya Aiba 1 1 Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan 2 Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan 3 Department of Dermatology, Faculty of University of Tsukuba, Tsukuba, Japan 4 Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan 5 Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan 6 Department of Dermatology, Keio University School of Medicine, Tokyo, Japan 7 Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan 8 Department of Dermatology, Wakayama Medical University, Wakayama, Japan 9 Department of Dermatology, Kyushu University Graduate School of Medicine, Fukuoka, Japan Correspondence to: Taku Fujimura, email: tfujimura1@mac.com Keywords: sCD163; CXCL5; TAMs; melanoma; POSTN Received: September 01, 2017      Accepted: February 10, 2018      Epub: February 15, 2018      Published: March 20, 2018 ABSTRACT Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists. The purpose of this study was to evaluate the value of using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced melanoma who were administered nivolumab. To this end, we analyzed these serum levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before nivolumab administration) and day 42. The serum absolute levels of sCD163 were significantly increased in patients who developed AEs ( p = 0.0018). Although there was no significant difference in serum levels of CXCL5, the absolute value of CXCL5 could at least be a supportive marker for the increased absolute levels of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab.