肿瘤细胞治疗研究
英文原题：Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer.
这些发现提示，CPS ≥ 1的患者由于其免疫微环境组成，可能对anti-PD-1/PD-L1治疗反应更好。
在KEYNOTE-811研究中，抗HER2和免疫治疗使CPS ≥ 1的HER2阳性胃癌患者生存期延长，而CPS < 1的患者缺乏显著获益。我们在一个106例HER2阳性、CPS < 1患者的真实世界队列中研究了这一问题，发现单独接受抗HER2治疗与加用免疫治疗的患者之间无生存差异。因此，我们研究了160例HER2阳性患者的肿瘤微环境变异，CPS ≥ 1病例表现出免疫细胞空间有效评分升高，包括CD4、CD8亚型和NK细胞，相较于CPS < 1。此外，通过对8例HER2阳性个体进行单细胞测序，基因表达揭示CPS ≥ 1病例中T细胞共刺激的调控以及CPS < 1病例中IL-1结合的调控。值得注意的是，我们发现了一种以CXCR4 + M2巨噬细胞为标志的CPS < 1亚型，与不良预后相关，其比例和表达在从抗HER2治疗中获益时降低。这些发现表明，CPS ≥ 1患者由于其免疫微环境组成，可能对抗PD-1/PD-L1治疗反应更好。
In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS < 1 patients lacked notable benefits. We studied this in a real-world cohort of 106 HER2-positive, CPS < 1 patients and found no survival differences between those treated with anti-HER2 therapy alone or with added immunotherapy. Thus, we investigate the tumor microenvironment variations in 160 HER2-positive patients, CPS ≥ 1 cases exhibited elevated spatial effective scores of immune cells, including CD4, CD8 subtypes, and NK cells, compared to CPS < 1. Furthermore, through single-cell sequencing in eight HER2-positive individuals, gene expressions revealed regulation of T-cell co-stimulation in CPS ≥ 1 and IL-1 binding in CPS < 1 cases. Notably, we discovered a CPS < 1 subtype marked by CXCR4 + M2 macrophages, associated with poor prognosis, whose proportion and expression were reduced when benefiting from anti-HER2 therapy. These findings suggest CPS ≥ 1 patients, due to their immune microenvironment composition, may respond better to anti-PD-1/PD-L1 therapy.
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