PD-1(+)CXCR5(-)CD4(+) Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma.
PD-1(+)CXCR5(-)CD4(+) Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma.
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PD-1( )CXCR5(-)CD4( ) Th-CXCL13细胞亚群驱动B细胞进入鼻咽癌三级淋巴结构
DOI：
10.1136/jitc-2020-002101
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发表时间：
2021-07
影响因子：
10.9
通讯作者：
Zhong Q
中科院分区：
文献类型：
--
作者：
Li JP;Wu CY;Chen MY;Liu SX;Yan SM;Kang YF;Sun C;Grandis JR;Zeng MS;Zhong Q
目前的一个主要挑战是利用三级淋巴样结构（TLSs）促进肿瘤抗原诱导的淋巴细胞浸润、活化和分化，以增强抗肿瘤免疫应答。TLS形成在针对鼻咽癌（NPC）的适应性免疫应答中的作用的机制在很大程度上仍然未知。通过单细胞RNA测序和荧光激活细胞分选分析鉴定细胞群体和相应的标记物。体外诱导分化实验模拟Th-CXCL 13细胞亚群在鼻咽癌肿瘤微环境中的产生、调节和功能。随后对肿瘤相关B细胞（TAB）和Th-CXCL 13细胞在TLS内的共定位进行组织学评价，并对TLS中的细胞与总存活率之间的关系进行统计学分析。在NPC中鉴定出PD-1+ CXCR 5 − CD 4 + Th-CXCL 13细胞亚群。该亚群是CXCL 13的主要来源，代表了大多数CD 4 + T细胞，其水平与TLS中存在的Th 1和Tfh细胞相当。由Toll样受体4激动剂激活的单核细胞充当最有效地触发Th-CXCL 13细胞扩增的抗原呈递细胞。转化生长因子β 1（Transforming growth factor beta 1，TGF-β1）的刺激和Sox 4的激活在此过程中对Th-CXCL 13细胞的诱导和极化至关重要。由Th-CXCL 13细胞募集的TAB的潜在功能性贡献证明了改善的存活率，Th-CXCL 13细胞通过TLSs中的白细胞介素-21和CD 84相互作用诱导浆细胞分化和免疫球蛋白产生。Th-CXCL 13细胞的诱导将先天性炎症与肿瘤相关TLS中的免疫赦免联系起来，并可能预测更好的生存率。
A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune responses against nasopharyngeal carcinoma (NPC) remain largely unknown. Cell populations and the corresponding markers were identified by single-cell RNA sequencing and fluorescence-activated cell sorting analysis. In vitro differentiation experiments were used to simulate the generation, regulation and function of the Th-CXCL13 cell subset in the tumor microenvironment of NPC. These were followed by histological evaluation of the colocalization of tumor-associated B cells (TABs) and Th-CXCL13 cells within TLSs, and statistical analysis of the relationship between the cells in TLSs and overall survival. A PD-1+CXCR5−CD4+ Th-CXCL13 cell subset was identified in NPC. This subset was a major source of CXCL13, representing the majority of the CD4+ T cells at levels comparable with Th1 and Tfh cells present in the TLSs. Monocytes activated by toll-like receptor 4 agonists served as the antigen-presenting cells that most efficiently triggered the expansion of Th-CXCL13 cells. Transforming growth factor beta 1 (TGF-β1) stimulation and activation of Sox4 were critical for the induction and polarization of Th-CXCL13 cells in this process. The potential functional contributions of TABs recruited by Th-CXCL13 cells which induced plasma cell differentiation and immunoglobulin production via interleukin-21 and CD84 interactions in the TLSs demonstrated improved survival. Induction of Th-CXCL13 cells links innate inflammation to immune privilege in tumor-associated TLSs and might predict better survival.
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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：
32.4
作者：
Joshi NS;Akama-Garren EH;Lu Y;Lee DY;Chang GP;Li A;DuPage M;Tammela T;Kerper NR;Farago AF;Robbins R;Crowley DM;Bronson RT;Jacks T
通讯作者：
Jacks T
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
DOI：
10.1164/rccm.201309-1611oc
发表时间：
2014-04-01
影响因子：
24.7
作者：
Germain, Claire;Gnjatic, Sacha;Dieu-Nosjean, Marie-Caroline
通讯作者：
Dieu-Nosjean, Marie-Caroline
影响因子：
25.7
作者：
Calderaro, Julien;Petitprez, Florent;Sautes-Fridman, Catherine
通讯作者：
Sautes-Fridman, Catherine