Immature tertiary lymphoid structure formation was increased in the melanoma tumor microenvironment of IKZF1 transgenic mice.
Immature tertiary lymphoid structure formation was increased in the melanoma tumor microenvironment of IKZF1 transgenic mice.
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在IKZF 1转基因小鼠的黑色素瘤肿瘤微环境中，未成熟的三级淋巴样结构形成增加。
DOI：
10.21037/tcr-22-1759
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发表时间：
2022-07
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
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作者：
IKZF1促进淋巴瘤的发生，也与乳腺癌、肝癌、卵巢癌的发生有关。假设IKZF1影响肿瘤免疫微环境中三级淋巴样结构（TLSs）的形成和发育，但IKZF1对肿瘤免疫微环境的影响尚未探讨。我们以黑色素瘤移植物为模型，研究IKZF1对黑色素瘤免疫微环境的影响。采用细胞计数试剂盒-8 （CCK8）检测IKZF1在黑色素瘤细胞中过表达对细胞增殖的影响。通过同源重组构建IKZF1过表达载体。线性化后，将过表达载体微注射到受精卵中。通过尾鉴定筛选过表达IKZF1的转基因小鼠。将黑色素瘤B16小鼠细胞消化成单细胞后，皮下植入C57BL6/ j -野生型（WT）小鼠和IKZF1转基因小鼠，比较两组小鼠的肿瘤生长情况。苏木精-伊红（HE）染色检测小鼠肿瘤组织中TLSs的数量。IKZF1在黑色素瘤细胞中的过表达不影响细胞增殖。成功构建IKZF1过表达载体pcDNA3.1-CAG-IKAROS。显微注射后获得有活力的受精卵。通过聚合酶链反应（PCR）鉴定出稳定表达IKZF1的转基因小鼠。与WT小鼠相比，IKZF1转基因小鼠的肿瘤负荷明显增加。HE染色显示，IKZF1转基因小鼠黑色素瘤中未成熟TLSs的数量明显增加。IKZF1不影响黑色素瘤细胞的增殖。成功构建了过表达IKZF1的转基因小鼠。IKZF1是未成熟TLS形成的关键驱动基因。
IKZF1 promotes the occurrence of lymphoma and is also related to the development of breast cancer, liver cancer, and ovarian cancer. It was hypothesized that IKZF1 influences tertiary lymphoid structures (TLSs) formation and development in the tumor immune microenvironment, and this effect of IKZF1 on the tumor immune microenvironment has not been explored. Using melanoma grafts as a model, we investigated the effect of IKZF1 on the immune microenvironment of melanoma. The Cell Count Kit-8 (CCK8) assay was used to detect the effect IKZF1 overexpression in melanoma cells on cell proliferation. The IKZF1 overexpression vector was constructed by homologous recombination. After linearization, the overexpression vector was microinjected into the fertilized egg. Transgenic mice overexpressing IKZF1 were screened by tail identification. After melanoma B16 mouse cells were digested into single cells, the tumor was subcutaneously implanted in C57BL6/J-wild type (WT) mice and IKZF1 transgenic mice, and the tumor growth of the 2 groups was compared. The number of TLSs in the tumor tissues of mice was analyzed after hematoxylin-eosin (HE) staining. Overexpression of IKZF1 in melanoma cells did not affect cell proliferation. The IKZF1 overexpression vector pcDNA3.1-CAG-IKAROS was successfully constructed. Viable fertilized eggs were obtained after microinjection. Transgenic mice stably expressing IKZF1 were identified by polymerase chain reaction (PCR). Compared with WT mice, the tumor load of IKZF1 transgenic mice increased significantly. HE staining showed that the number of immature TLSs in melanomas of IKZF1 transgenic mice increased significantly. IKZF1 does not affect the proliferation of melanoma cells. Transgenic mice overexpressing IKZF1 were successfully constructed. IKZF1 is a key driver gene of the formation of immature TLS.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
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：
7.3
作者：
Albini A;Bruno A;Noonan DM;Mortara L
通讯作者：
Mortara L
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
25.7
作者：
Calderaro, Julien;Petitprez, Florent;Sautes-Fridman, Catherine
通讯作者：
Sautes-Fridman, Catherine