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-DRlowmonocytes), 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-DRlowmonocytes 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.
确定哪些基线特征能使癌症患者从免疫检查点抑制剂治疗中获得最大获益，仍是一个重要挑战。此外，生物标志物有助于在初始治疗应答后选择最佳治疗时长。本项初步研究追踪了12例接受免疫检查点抑制剂联合化疗的晚期非小细胞肺癌患者中四种不同免疫细胞参数的时间变化，这些患者均生存至少12个月。分别在首次和第三次抗体给药时点，以及患者生存满12个月时采集血液样本。通过多色流式细胞术检测了两类抑制性标志物（中性粒细胞/淋巴细胞比值及循环HLA-DRlow单核细胞频率），以及两类反映持续免疫应答的标志物（6-磺基乳糖胺非经典单核细胞和树突状细胞亚群）。在大多数生存超过12个月的患者中，观察到较低的中性粒细胞/淋巴细胞比值和较少的HLA-DRlow单核细胞，同时伴有明确可检测的6-磺基乳糖胺非经典单核细胞和树突状细胞亚群。其中两例患者出现抑制性标志物升高，同时伴随6-磺基乳糖胺非经典单核细胞和树突状细胞亚群减少，这至少在一例患者中与持续临床进展相关。我们的研究结果表明，中性粒细胞/淋巴细胞比值、特定单核细胞亚群及血液树突状细胞数量，可能成为癌症患者接受免疫检查点抑制剂联合化疗长期治疗过程中具有预测价值的生物标志物。
肿瘤(癌症)患者之家