Supplementary Material for: Serum CCL22 Increased in Advanced Melanoma Patients with Liver Metastases: Report of 5 Cases

Advanced melanoma patients with liver metastases show a limited response to immunotherapy by the induction of regulatory T cells and depletion of effector cells, which leads to a poor prognosis. Tumor-associated macrophages (TAMs) induce apoptosis of activated antigen-specific CD8+ T cells in melanomas, leading to induction of tolerance to immune checkpoint inhibitors. In addition, TAMs produce various chemokines, and several serum pro-inflammatory chemokines measured at baseline are useful for the prediction of the efficacy of immunomodulatory drugs. In this study, serum levels of CCL22, CXCL5, and CXCL10 were evaluated by ELISA at baseline in 10 melanoma patients, 5 with liver metastases and 5 with lung metastases, treated with anti-PD1 Abs. Serum levels of CCL22, but not CXCL5 and CXCL10, were increased in patients with liver metastases compared to those with lung metastases or historical controls. The present data suggest that elevated serum CCL22 levels might be a biomarker for liver metastases in melanoma patients.

伴肝转移的晚期黑色素瘤患者，因调节性T细胞（regulatory T cells）诱导与效应细胞（effector cells）耗竭，对免疫治疗应答有限，预后较差。肿瘤相关巨噬细胞（Tumor-associated macrophages, TAMs）可诱导黑色素瘤中活化的抗原特异性CD8+ T细胞（CD8+ T cells）凋亡，进而引发免疫检查点抑制剂耐受。此外，TAMs可分泌多种趋化因子；基线状态下检测的数种血清促炎性趋化因子，可用于预测免疫调节药物的治疗疗效。本研究采用酶联免疫吸附测定（ELISA），在基线状态下对10例接受抗PD-1抗体（anti-PD1 Abs）治疗的黑色素瘤患者的血清CCL22、CXCL5与CXCL10水平进行了检测；其中5例伴肝转移，5例伴肺转移。与肺转移患者或历史对照人群相比，伴肝转移患者的血清CCL22水平升高，而CXCL5与CXCL10水平无显著变化。本研究数据提示，血清CCL22水平升高或可作为黑色素瘤患者伴肝转移的生物标志物。