Université de Paris, PARCC, INSERM, 75015, Paris, France.
Hôpital Européen Georges-Pompidou, APHP; Department of GI oncology, Université de Paris, Paris, France.
Gastric Cancer. 2020 Jan;23(1):73-81. doi: 10.1007/s10120-019-00983-3. Epub 2019 Jul 2.
The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown.
Circulating natural killer (NK) cells, CD4 and CD8 T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were quantified in peripheral blood mononuclear cells (PBMCs) from 67 patients with untreated AGC enrolled in the PRODIGE 17-ACCORD 20 trial. CD56 cells (NK), CD8, and FoxP3 (Treg) tumor-infiltrating lymphocytes (TILs) were assessed in tumor samples.
Circulating NK and Treg proportions were significantly lower in patients with diffuse/mixed-type AGC (n = 27) than those with intestinal type (n = 40; median 6.3% vs 11.5%; p = 0.02 and median 3.3% vs 5.2%; p = 0.03, respectively). Proportions of circulating MDSC, CD4 and CD8 T cells were not associated with one pathological type. Among tumor-infiltrating cells, CD8 T cells, but not NK or FoxP3 cells, were significantly lower in diffuse/mixed-type AGC (median 21 vs 59 cells/field; p = 0.009). Patients with high circulating NK cell counts (> 17%) had a better overall survival than those with < 17% (HR 0.40; 95% CI [0.15-1.06]; p = 0.04). Patients with high CD8 TIL counts (> 31 cells/field) had significantly longer overall survival (HR 0.44; 95% CI [0.21-0.92]; p = 0.02). The prognostic value of CD8 TILs was maintained after adjustment for confounding factors, including the Lauren classification (HR = 0.42; 95% CI [0.18-0.96]; p = 0.039).
Diffuse/mixed-type AGC has lower rates of CD8 TILs and circulating NK cells and Tregs than the intestinal type. This "cold tumor" phenotype may be associated with a worse outcome.
免疫细胞与 Lauren 分类亚型之间的相关性及其对晚期胃癌（AGC）的预后影响尚不清楚。
在 PRODIGE 17-ACCORD 20 试验中，对 67 例未经治疗的 AGC 患者的外周血单核细胞（PBMC）中循环自然杀伤（NK）细胞、CD4 和 CD8 T 细胞、调节性 T 细胞（Tregs）和髓系来源的抑制细胞（MDSCs）进行定量检测。在肿瘤样本中评估 CD56 细胞（NK）、CD8 和 FoxP3（Treg）肿瘤浸润淋巴细胞（TIL）。
弥漫型/混合型 AGC（n=27）患者的循环 NK 和 Treg 比例明显低于肠型（n=40；中位数 6.3%比 11.5%；p=0.02 和中位数 3.3%比 5.2%；p=0.03，分别）。循环 MDSC、CD4 和 CD8 T 细胞的比例与一种病理类型无关。在肿瘤浸润细胞中，弥漫型/混合型 AGC 患者的 CD8 T 细胞（中位数 21 比 59 个细胞/视野；p=0.009），而 NK 或 FoxP3 细胞则明显降低。循环 NK 细胞计数较高（>17%）的患者总生存时间优于计数较低的患者（HR 0.40；95%CI [0.15-1.06]；p=0.04）。CD8 TIL 计数较高（>31 个细胞/视野）的患者总生存时间明显延长（HR 0.44；95%CI [0.21-0.92]；p=0.02）。在调整混杂因素，包括 Lauren 分类后，CD8 TIL 的预后价值仍然存在（HR=0.42；95%CI [0.18-0.96]；p=0.039）。
弥漫型/混合型 AGC 的 CD8 TIL 和循环 NK 细胞和 Tregs 比率低于肠型。这种“冷肿瘤”表型可能与预后较差有关。
