Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Cancer Sci. 2020 Aug;111(8):3032-3044. doi: 10.1111/cas.14495. Epub 2020 Jul 20.
Tumor location and immunity play important roles in the progression of colorectal cancer (CRC). This study aimed to investigate the differences in the immunosurveillance pattern between right- and left-sided CRC and analyze their association with clinicopathologic features, including mismatch repair (MMR) status. We included surgically resected stage II/III CRC cases and evaluated the immunohistochemical findings of HLA class I, HLA class II, programmed cell death-ligand 1 (PD-L1), PD-1, CTLA-4, CD3, CD4, CD8, TIA-1, T-bet, GATA3, RORγT, Foxp3, and CD163. A total of 117 patients were included in the analyses; of these, 30 and 87 had right- and left-sided cancer, respectively. Tumor immunity varied according to the tumor location in the overall cohort. Analysis of the tumors excluding those with DNA mismatch repair (MMR) deficiency also revealed that tumor immunity differed according to the tumor location. In right-sided colon cancer (CC), high expression of Foxp3 (P = .0055) and TIA-1 (P = .0396) were associated with significantly better disease-free survival (DFS). High CD8 (P = .0808) and CD3 (P = .0863) expression tended to have better DFS. Furthermore, in left-sided CRC, only high PD-L1 expression in the stroma (P = .0426) was associated with better DFS. In multivariate analysis, high Foxp3 expression in right-sided CC was an independent prognostic factor for DFS (hazard ratio, 7.6445; 95% confidence interval, 1.2091-150.35; P = .0284). In conclusion, the immunosurveillance pattern differs between right- and left-sided CRC, even after adjusting for MMR deficiency.
肿瘤位置和免疫在结直肠癌（CRC）的进展中起着重要作用。本研究旨在探讨左右侧 CRC 之间免疫监视模式的差异，并分析其与临床病理特征（包括错配修复（MMR）状态）的关系。我们纳入了手术切除的 II/III 期 CRC 病例，并评估了 HLA Ⅰ类、HLA Ⅱ类、程序性细胞死亡配体 1（PD-L1）、PD-1、细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）、CD3、CD4、CD8、T 细胞内抗原 1（TIA-1）、T 细胞转录因子（T-bet）、GATA 结合蛋白 3（GATA3）、维甲酸相关孤核受体γt（RORγT）、叉头框 P3（Foxp3）和 CD163 的免疫组织化学检测结果。共有 117 例患者纳入分析，其中 30 例和 87 例分别为右侧和左侧癌症。在整个队列中，肿瘤免疫因肿瘤位置而异。在排除 DNA 错配修复（MMR）缺陷的肿瘤后进行分析，也发现肿瘤免疫因肿瘤位置而异。在右侧结肠癌（CC）中，Foxp3（P=0.0055）和 TIA-1（P=0.0396）高表达与显著更好的无病生存（DFS）相关。高 CD8（P=0.0808）和 CD3（P=0.0863）表达有更好的 DFS 趋势。此外，在左侧 CRC 中，只有基质中高 PD-L1 表达（P=0.0426）与更好的 DFS 相关。在多变量分析中，右侧 CC 中 Foxp3 高表达是 DFS 的独立预后因素（风险比，7.6445；95%置信区间，1.2091-150.35；P=0.0284）。总之，即使调整 MMR 缺陷后，左右侧 CRC 之间的免疫监视模式也不同。
