Modulation of Inflammatory Proteins in Serum May Reflect Cutaneous Immune Responses in Cancer Immunotherapy.
Modulation of Inflammatory Proteins in Serum May Reflect Cutaneous Immune Responses in Cancer Immunotherapy.
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DOI：
10.1016/j.xjidi.2022.100179
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Gulati N
中科院分区：
文献类型：
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作者：
Han J;Correa da Rosa J;Agarwal A;Owji S;Yassky D;Luu Y;Shah A;Estrada Y;Ungar J;Sarin KY;Krueger JG;Gulati N
Diphencyprone (DPCP) 是一种局部接触性增敏剂，已显示出治疗皮肤黑色素瘤转移的功效，包括有时超出直接治疗部位的转移，但指示治疗反应的生物标志物尚未得到表征。因此，我们对 5 名皮肤黑色素瘤转移患者在治疗过程的第 0、63 和 112 天进行了皮肤和血清的蛋白质组分析，这些患者接受 DPCP 治疗。在血清中，我们发现 96 种评估的免疫肿瘤蛋白中有 13 种在 DPCP 治疗后显着上调 (P < 0.05)。上调的蛋白包括T辅助1轴蛋白（CXCL9、CXCL10）、免疫检查点蛋白（PD-1）以及各种具有促进肿瘤免疫作用的蛋白，例如CD80和TNFRSF4/9。鉴于所研究的 5 名患者对局部治疗的积极临床反应，这些蛋白质可能代表血清中的预后生物标志物，用于评估 DPCP 治疗皮肤黑色素瘤转移的疗效。由于 DPCP 不会导致免疫检查点抑制剂所见的非特异性免疫相关不良事件，因此我们的研究为局部 DPCP 引起的潜在肿瘤特异性全身免疫激活和全身抗肿瘤效应提供了证据。
Diphencyprone (DPCP), a topical contact sensitizer, has shown 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 on 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 after DPCP treatment. Upregulated proteins included those of the T helper 1 axis (CXCL9, CXCL10), immune checkpoint proteins (PD-1), and various proteins with roles in promoting tumor immunity such as CD80 and TNFRSF4/9. 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 DPCP treatment of cutaneous melanoma metastases. Because DPCP does not lead to nonspecific immune-related adverse events seen with immune checkpoint inhibitors, our study provides evidence for potential tumor-specific systemic immune activation and systemic antitumor effectors elicited by topical DPCP.