Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
Dig Dis Sci. 2021 Feb;66(2):474-482. doi: 10.1007/s10620-020-06203-8. Epub 2020 Mar 19.
Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood.
Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon's signed rank test.
All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069).
The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.
肝转移是结直肠癌患者对免疫治疗反应不良的标志。然而，原发肿瘤和肝转移瘤之间的免疫微环境差异尚未得到很好的理解。
对 54 例接受原发和转移病灶切除术的结直肠癌伴肝转移患者进行了分析。免疫评分基于肿瘤中心和边缘浸润免疫细胞（CD3+细胞、CD8+细胞、CD11b+细胞、CD11c+细胞和 CD33+细胞）的密度。使用 Wilcoxon 符号秩检验分析原发肿瘤和肝转移灶中免疫标志物的表达。
在原发肿瘤和肝转移灶中，所有 5 种标志物在肿瘤边缘的表达均高于中心肿瘤。CD11c 和 CD11b 在转移灶和原发肿瘤之间的表达无差异。在肿瘤边缘，除 CD11b 外，其余 4 种标志物在肝转移灶中的表达均明显高于原发肿瘤。在肿瘤内，CD3 在原发肿瘤中的表达高于肝转移灶，而 CD33 在肝转移灶中的表达高于原发肿瘤。原发肿瘤中总 CD8+细胞中 CD8+ CD3+细胞的比例明显高于肝转移灶（36.42%比 24.88%，p=0.0069）。
原发肿瘤和肝转移瘤之间的免疫微环境不同。肝脏中更多的免疫抑制细胞可能部分解释了为什么结肠癌的免疫治疗对肝转移疾病的效果较差。
