Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
Br J Cancer. 2020 Apr;122(9):1399-1408. doi: 10.1038/s41416-020-0793-y. Epub 2020 Mar 17.
The aim of the study was to determine the human leucocyte antigen class-I (HLA-I), programmed death-ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) of microsatellite instability-high gastric cancer.
The HLA-I expression type was determined by immunohistochemistry of HLA-A, HLA-B, HLA-C and β2-microglobulin in the centre of the tumour (CT) and in the invasive margin (IM) of samples from 293 patients (total loss vs. preserved type). PD-L1 expression and TIL density was examined immunohistochemically. HLA-I genotyping was also performed.
The expression loss of the HLA-I molecules was significantly associated with low TIL density. According to survival analyses, the HLA-I expression type and PD-L1 positivity were not independent prognostic factors. The TIL density had no prognostic implication when survival analysis was performed for the whole patient group; however, high CD8 TIL infiltration was significantly associated with good prognosis in only HLA-I-preserved-type/PD-L1-positive group (p = 0.034). The homozygosity of the HLA-I allele was more frequently observed in the total loss type group.
We confirmed differential prognostic implication of CD8 TILs according to the HLA-I and PD-L1 expression. Determination of the HLA-I expression could be helpful to select patients who would benefit from anti-PD-1/PD-L1 therapy.
本研究旨在确定微卫星不稳定高型胃癌的人类白细胞抗原 I 类（HLA-I）、程序性死亡配体 1（PD-L1）表达和肿瘤浸润淋巴细胞（TIL）。
通过免疫组化检测 293 例患者肿瘤中心（CT）和侵袭边缘（IM）样本中 HLA-A、HLA-B、HLA-C 和β2-微球蛋白的 HLA-I 表达类型（总缺失型与保留型）。采用免疫组化检测 PD-L1 表达和 TIL 密度。同时还进行了 HLA-I 基因分型。
HLA-I 分子表达缺失与 TIL 密度低显著相关。生存分析显示，HLA-I 表达类型和 PD-L1 阳性不是独立的预后因素。在对所有患者进行生存分析时，TIL 密度无预后意义；然而，在 HLA-I 保留型/PD-L1 阳性组中，高 CD8 TIL 浸润与良好预后显著相关（p=0.034）。总缺失型组中 HLA-I 等位基因的纯合性更为常见。
我们证实了 CD8 TIL 根据 HLA-I 和 PD-L1 表达的不同预后意义。HLA-I 表达的测定有助于选择可能从抗 PD-1/PD-L1 治疗中获益的患者。
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