Möller Miriam, Schütte Wolfgang, Turzer Steffi, Seliger Barbara, Riemann Dagmar
Clinic of Internal Medicine, Hospital Martha-Maria Halle-Dölau, 06120 Halle, Germany.
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany.
Cancers (Basel). 2023 Oct 6;15(19):4873. doi: 10.3390/cancers15194873.
An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients' survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DR monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DR monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy.
确定最能从免疫检查点抑制剂(ICI)治疗中获益的癌症患者的基线特征仍然是一项重大挑战。此外,生物标志物有助于在初次治疗反应后选择最佳治疗持续时间。在这项前瞻性研究中,对12例接受ICI治疗联合化疗且存活至少12个月的晚期非小细胞肺癌(NSCLC)患者的四种不同免疫细胞参数的时间进程进行了跟踪。在首次和第三次抗体给药时以及患者存活12个月后采集血液。使用多色流式细胞术测定了两种抑制性标志物(中性粒细胞/淋巴细胞比率(NLR)和循环HLA - DR单核细胞频率)以及两种正在进行的免疫反应标志物(6 - 磺基乳糖胺(slan)+非经典单核细胞和树突状细胞(DC)亚型)。在大多数存活超过12个月的患者中,观察到低NLR和低数量的HLA - DR单核细胞,同时slan +非经典单核细胞和DC亚型数量明显可检测。两名患者的抑制性标志物增加,同时slan +非经典单核细胞和DC亚型减少,其中至少一名患者的这种情况与持续的临床进展相关。我们的结果表明,NLR、单核细胞的特定亚型以及血液DC数量可能是癌症患者在ICI/化疗长期治疗期间有用的预测生物标志物。