Modulation of Inflammatory Proteins in Serum May Reflect Cutaneous Immune Responses in Cancer Immunotherapy

Diphencyprone (DPCP), a topical contact sensitizer, has demonstrated efficacy in treating cutaneous melanoma metastases, including at times beyond the directly treated sites, but biomarkers indicative of treatment response have not been characterized. Thus, we performed a proteomic analysis of the skin and serum of five patients with cutaneous melanoma metastases treated with DPCP at days 0, 63, and 112 of the treatment course. In the serum, we found a significant upregulation (P<0.05) in 13 of 96 assessed immuno-oncology proteins following DPCP treatment. Upregulated proteins included those of the Th1 axis (CXCL9, CXCL10), immune checkpoint proteins (PD1), and various proteins with roles in promoting tumor immunity such as CD80 and TNF receptor superfamily 4/9. Given the positive clinical response to topical treatment noted in the five patients studied, these proteins may represent prognostic biomarkers in the serum for evaluating the efficacy of diphencyprone treatment of cutaneous melanoma metastases. As DPCP does not lead to non-specific immune-related adverse events seen with immune checkpoint inhibitors, our study provides evidence for potential tumor-specific systemic immune activation and systemic anti-tumor effectors elicited by topical DPCP.