Tertiary lymphoid structure and decreased CD8(+) T cell infiltration in minimally invasive adenocarcinoma.
Tertiary lymphoid structure and decreased CD8(+) T cell infiltration in minimally invasive adenocarcinoma.
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微创腺癌中的三级淋巴结构和 CD8 T 细胞浸润减少
DOI：
10.1016/j.isci.2022.103883
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发表时间：
2022-03-18
期刊：
影响因子：
5.8
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Wang J;Jiang D;Zheng X;Li W;Zhao T;Wang D;Yu H;Sun D;Li Z;Zhang J;Zhang Z;Hou L;Jiang G;Fei K;Zhang F;Yang K;Zhang P
缺乏对早期肺癌患者的肿瘤微环境（TME）的了解，尤其是与匹配的邻近组织相比，缺乏表征早期肺腺癌的TME。 （MIA）肿瘤和相邻的正常组织。激活和低CD8+ T细胞浸润。 TLS）形成。多重免疫组织化学染色验证了TLS的形成，并揭示了TLS卵泡中卵泡调节T细胞（TFR）的富集，这可以解释较低的CD8+ T细胞浸润和MIA中的抗肿瘤免疫学减弱。
B和CD4+ T细胞的更高浸润和激活表征了MIA肿瘤
MIA肿瘤用CD8+ T细胞低于正常组织渗透
由B，CD4+ T细胞和CD35+ FDC构成的TLS在MIA肿瘤中得到验证
CD8+ T减少与MIA肿瘤中TFR介导的免疫抑制有关
免疫力；
Knowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4+ T cell infiltration, high B-cell activation, and low CD8+ T cell infiltration. The high expression of markers for B cells, activated CD4+ T cells, and follicular helper T (Tfh) cells in bulk MIA samples and three independent single-cell RNA-seq datasets implied tertiary lymphoid structures (TLS) formation. Multiplex immunohistochemistry staining validated TLS formation and revealed an enrichment of follicular regulatory T cells (Tfr) in TLS follicles, which may explain the lower CD8+ T cell infiltration and attenuated anti-tumor immunity in MIA. Our study demonstrates how integrating transcriptome and pathology characterize TME and elucidate potential mechanisms of tumor immune evasion. Higher infiltration and activation of B and CD4+ T cell characterize MIA tumors MIA tumors are infiltrated with lower CD8+ T cells than normal tissues TLS constituted by B, CD4+ T cells, and CD35+ FDC is validated in MIA tumors Decreased CD8+ T is associated with Tfr-mediated immunosuppression in MIA tumor Immunity; Components of the immune system; Cancer
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
5.2
作者：
Bergomas F;Grizzi F;Doni A;Pesce S;Laghi L;Allavena P;Mantovani A;Marchesi F
通讯作者：
Marchesi F
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.5
作者：
Finkin S;Yuan D;Stein I;Taniguchi K;Weber A;Unger K;Browning JL;Goossens N;Nakagawa S;Gunasekaran G;Schwartz ME;Kobayashi M;Kumada H;Berger M;Pappo O;Rajewsky K;Hoshida Y;Karin M;Heikenwalder M;Ben-Neriah Y;Pikarsky E
通讯作者：
Pikarsky E
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