Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases.
Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases.
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原发性结直肠癌与肝转移瘤免疫微环境的多视角比较
DOI：
10.1186/s12967-022-03667-2
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发表时间：
2022-10-04
影响因子：
7.4
通讯作者：
Lu, Yuanyuan
中科院分区：
文献类型：
--
作者：
He, Yangsong;Han, Yanan;Fan, A-Hui;Li, Danxiu;Wang, Boda;Ji, Kun;Wang, Xin;Zhao, Xiaodi;Lu, Yuanyuan
肝转移是结直肠癌患者免疫治疗反应差的主要原因。然而，原发肿瘤和肝转移瘤在免疫微环境方面的区别并不能很好地描述。本研究的目的是比较多种免疫细胞的表达谱，以进一步分析肝转移瘤和原发肿瘤微环境的异同。应用多光谱免疫荧光技术对17例结直肠癌原发灶和肝转移灶切除后的组织进行了分析。比较多种免疫细胞(CD8、Foxp3、CD68、CD163、CD20、CD11c、CD66b、CD56、PD-L1、INF-γ、Ki67和VEGFR-2)在肿瘤中心(TC)、肿瘤侵袭前沿(<； ，Tf)和瘤周(≥ ，PT)的表达。细胞共定位法进一步分析CD68和CD163在不同区域的表达情况。此外，根据CD8的浸润程度对不同的免疫表型进行了研究和比较。12种标志物在原发灶和肝转移灶中的表达趋势基本一致。然而，与Tf区和PT区相比，CD163在原发灶和肝转移灶中的表达趋势并不一致，尤其是CD163，它在PT区比在Tf区更高表达。在不同空间分布的对比中，CD163在肝转移灶中的表达高于原发灶。CD68和CD163共定位的进一步分析表明，巨噬细胞在肝转移灶中的分布与原发灶有显著差异，肝转移灶中以CD68−CD163+巨噬细胞为主。此外，在免疫排斥表型中，CD163的表达最高。在原发结直肠癌和肝转移癌中发现的免疫细胞在空间分布上有所不同。肝转移瘤中存在更多的免疫抑制细胞，其中巨噬细胞的差异分布最为明显。CD68、−、CD163+巨噬细胞可能与肝内免疫抑制、免疫治疗作用弱有关。网上版载有补充材料，可在10.1186/s12967-022-03667-2查阅。
Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects. The online version contains supplementary material available at 10.1186/s12967-022-03667-2.
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影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
6.2
作者：
Shi, Ju-Fang;Wang, Le;He, Jie
通讯作者：
He, Jie
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影响因子：
--
作者：
Ni, Yan-Hong;Ding, Liang;Hou, Ya-Yi
通讯作者：
Hou, Ya-Yi
影响因子：
10.9
作者：
Sater, Houssein Abdul;Marte, Jennifer L.;Gulley, James L.
通讯作者：
Gulley, James L.
影响因子：
4.6
作者：
Shang B;Liu Y;Jiang SJ;Liu Y
通讯作者：
Liu Y