Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
German Cancer Consortium (DKTK), Partner Site Mainz/Frankfurt am Main, Mainz, Germany.
Cancer Med. 2021 Mar;10(5):1562-1575. doi: 10.1002/cam4.3710. Epub 2021 Jan 15.
Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy.
This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count.
Responders to ICI therapy displayed an abundance of proliferating CD4 T cells, an increased lymphocyte-to-monocyte ratio, a low platelet-to-lymphocyte ratio, low levels of CTLA-4 Treg, and (arginase 1 ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). Nevertheless, non-responders with similar immune cell compositions also benefited from therapy displaying increased long-term OS.
Our study demonstrated that the observed immune signature in the peripheral blood of melanoma patients prior to treatment could identify responders as well as non-responders that benefit from ICI immunotherapies.
恶性黑色素瘤是一种具有免疫原性的皮肤癌，其全球发病率呈上升趋势。黑色素瘤的晚期预后较差。目前，尚无可靠的参数可以预测患者对免疫检查点抑制剂（ICI）治疗的反应。
本研究强调了血液中独特免疫特征对于 ICI 治疗反应和总生存期（OS）的相关性。因此，通过流式细胞术和全血细胞计数分析了 45 例黑色素瘤患者在 ICI 治疗前外周血中的免疫细胞组成。
ICI 治疗的应答者表现出大量增殖的 CD4 T 细胞、淋巴细胞与单核细胞比值增加、血小板与淋巴细胞比值降低、CTLA-4 Treg 水平降低以及（精氨酸酶 1）中性粒细胞骨髓来源的抑制性细胞（PMN-MDSC）减少。然而，具有相似免疫细胞组成的非应答者也从治疗中获益，显示出长期 OS 的增加。
我们的研究表明，在治疗前黑色素瘤患者外周血中观察到的免疫特征可以识别应答者和非应答者，这些患者可从 ICI 免疫治疗中获益。
