Antibodies against PD1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with a high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate the nivolumab efficacy to avoid serious irAEs caused by ipilimumab. 
Notably, PD-1 expression is a key factor in maintaining CD163+TAMs as M2-polarized, and blockade of PD-1/PD-L1 leads to conversion of TAMs into M1-polarized activated macrophages, leading to the release of sCD163 and other TAMs related chemokines (e.g. CXCL5, CXCL10, CCL22) in serum. From the above findings, in this study we analyzed the serum levels of sCD163 as well as CXCL5, CXCL10 and CCL22 in 75 cases of advanced melanoma using anti-PD1 antibodies. The serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after the initial administration of nivolumab for cutaneous melanoma. Moreover, high baseline serum levels of CXCL5 correlated with the objective response to nivolumab in patients with advanced melanoma, whereas there were no significant relationships between the serum levels of CXCL10 and CCL22. These results suggest that sCD163 in combination with CXCL5 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

Serum level of tumor-associated macrophage (TAMs)-related factors may be a predictive marker of the effectiveness of nivolumab in patients with advanced cutaneous melanoma