MRI表观弥散系数预测肝细胞癌肿瘤免疫细胞浸润
Apparent Diffusion Coefficient of MRI in Predicting the Immune Microenvironment of HCC
- 中山大学学报（医学科学版） 2021年42卷第2期 页码：242-249
- 作者机构：
中山大学附属第一医院放射诊断专科，广东 广州 510058
- 作者简介：
黄梦琪，在读博士生，研究方向：腹部影像学，E-mail:mqhuang0702@163.com
- 基金信息：国家自然科学基金(81971684)
DOI：
中图分类号： R735.7;R445.2纸质出版日期：2021-03-20，
收稿日期：2021-01-21，
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黄梦琪,宋晨宇,林映宇等.MRI表观弥散系数预测肝细胞癌肿瘤免疫细胞浸润[J].中山大学学报（医学科学版）,2021,42(02):242-249.
HUANG Meng-qi,SONG Chen-yu,LIN Ying-yu,et al.Apparent Diffusion Coefficient of MRI in Predicting the Immune Microenvironment of HCC[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(02):242-249.
摘要
目的
2
探索MRI弥散加权成像（DWI）的表观弥散系数（ADC）评估肝细胞癌（HCC）免疫细胞浸润的可行性。
方法
2
纳入初治HCC患者24例，所有患者均于术前行MRI DWI检查。收集患者术后1 h内新鲜组织块，分别取瘤内、瘤旁2 cm内组织块。采用多色流式细胞分析术获得组织内炎性细胞、T细胞、B细胞、CD4
+
T细胞、CD8
+
T细胞以及CD8
+
PD1
+
T细胞、调节性T细胞、巨噬细胞比率。在MRI ADC图上测量肿瘤ADC值、瘤旁肝组织ADC值（pADC），计算肿瘤比瘤旁组织相对ADC值（rADC）。采用Pearson’s相关系数分析ADC值与肿瘤、瘤旁肝组织免疫细胞浸润的相关性。
结果
2
肿瘤和瘤旁肝组织免疫细胞数量存在差异，与瘤旁肝组织相比，瘤内CD45+细胞数量偏少（18.39%
vs
. 25.38%，
P
= 0.026），而CD8
+
PD1
+
T细胞明显偏高（46.22%
vs
. 18.78%，
P
<
0.001），此外瘤内调节T细胞数量亦明显偏高（3.29%
vs.
2.01%，
P
=0.010）。ADC与多类疫细胞比例具相关性，rADC与瘤内CD4
+
T细胞比率呈正相关（
r
＝0.523，
P
＝0.009）、与瘤旁PD1
+
Tc细胞呈正相关（
r
＝0.535，
P
＝0.007），肿瘤ADC值与瘤旁CD19
+
B细胞呈负相关（
r
＝-0.476，
P
＝0.019），pADC值与PD1
＋
效应T细胞呈负相关（
r
＝-0.410，
P
＝0.047）。
结论
2
HCC肿瘤与瘤旁肝组织免疫浸润微环境存在差异，MRI ADC值可以无创性评估肿瘤、瘤旁肝组织免疫浸润情况。
Abstract
Objective
2
This study intends to explore the feasibility of MRI apparent diffusion coefficient in evaluating the immune infiltration of hepatocellular carcinoma.
Methods
2
Twenty-four initially treated patients with HCC were included. Fresh tissues were collected within 1 hour after surgery， and the peritumoral liver tissues within 2 cm and tumor tissues were collected respectively with the size of 1.0 cm×0.5 cm×0.3 cm. The ratio of CD45
+
inflammatory cells， CD3
+
T cells， CD19
+
B cells， CD4
+
T cells， CD8
+
effector T cells and PD1
+
effector T cells， regulatory T cells and macrophages in the corresponding tissues were obtained by multicolor flow cytometry. Two experienced radiologist measured the Apparent Diffusion Coefficient （ADC） of liver tumor and the ADC value of adjacent liver tissue （pADC） on the Apparent Diffusion Coefficient mapping， and calculated the relative ADC value of tumor to adjacent liver tissue （rADC）. Pearson's correlation analysis was used to test the correlation between ADC and immune cell infiltration of the tumor and adjacent liver.
Results
2
There was statistically significant difference of the immune cell ratio between the peritumoral liver tissue and tumor， CD45
+
leukocytes of the tumor were less than the peritumoral liver tissue （18.39%
vs
. 25.38%，
P
=0.026）， while CD8
+
PD1
+
T cells were notably higher （46.22%
vs
. 18.78%，
P
<
0.001）. In addition， the Treg cell ratio was also significantly higher than that of the adjacent liver （3.29%
vs
. 2.01%，
P
=0.010）， which indicate more severe immune suppression. Pearson's correlation analysis suggest that the diffusion weighted parameters were associated with the immune cell infiltration. The rADC was positively correlated with CD4
+
T cells （
r
＝0.523，
P
＝0.009） and peritumoral PD1
+
effector T cells （
r
＝0.535，
P
＝0.007）. The ADC was negatively correlated with peritumoral CD19
+
B cells （
r
＝-0.476，
P
＝0.019）. In addition， the pADC value was negatively correlated with PD1
+
effector T cells of the tumor（
r
＝-0.410，
P
＝0.047）. Which indicated that the severity of the diffusion limitation in tumor and peritumoral liver parenchymal was correlated with the tumor immunosuppressive microenvironment.
Conclusion
2
There are differences in the immune microenvironment between hepatocellular carcinoma and adjacent liver. MRI diffusion parameters can provide noninvasive assessment of immune microenvironment.
关键词
肝细胞癌肿瘤免疫磁共振弥散成像
Keywords
hepatocellular carcinomatumor immunitymagnetic resonance imagingdiffusion weighted imaging
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