Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Korea.
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Korea.
Cancer Sci. 2021 Jan;112(1):91-100. doi: 10.1111/cas.14723. Epub 2020 Nov 28.
Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability-high (MSI-H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2-microglobulin (β2M) expression in MSI-H and microsatellite-stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI-H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI-H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI-H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI-H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy-naive MSI-H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC.
人类白细胞抗原（HLA）I 类的下调被认为是各种肿瘤，特别是微卫星不稳定高（MSI-H）结直肠癌（CRC）中适应性免疫逃逸的一种机制。在这项研究中，我们旨在研究 MSI-H 和微卫星稳定（MSS）CRC 中 HLA I 类和β2-微球蛋白（β2M）的表达，并确定其预后影响。从 300 例 CRC 中选择肿瘤中心（TC）和肿瘤外周（TP）的代表性区域，包括 161 例 MSI-H 和 139 例 MSS 病例，构建组织微阵列。进行 HLA A/B/C、β2M、CD3 和 CD8 的免疫组织化学（IHC）染色。在 113 例（70.2%）MSI-H 和 54 例（38.8%）MSS 病例中检测到 HLA A/B/C 表达降低，而在 69 例（42.9%）MSI-H 和 17 例（12.2%）MSS 病例中检测到β2M 表达降低。虽然在具有边缘意义的 MSI-H CRC 中，β2M 表达降低与较高的病理肿瘤（pT）分期相关，但在 HLA A/B/C 和β2M 表达与生存之间未发现相关性。有趣的是，在 MSS 中 HLA A/B/C 表达降低与较高的分期相关，并且在多变量分析中 HLA A/B/C 和β2M 表达降低是独立的预后因素。总之，在免疫治疗初治的 MSI-H CRC 中经常观察到 HLA A/B/C 和β2M 表达降低，这表明对免疫检查点抑制剂存在原发性耐药的可能性。有趣的是，HLA A/B/C 和β2M 的下调与 MSS 癌症的不良预后相关。总体而言，HLA A/B/C 和β2M 的 IHC 可能是 CRC 中一种可行的预测或预后工具。
