Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors.
Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors.
复制标题
用新辅助免疫检查点抑制剂治疗的可切除肺癌中肿瘤淋巴结的多尺度表征。
DOI：
10.1016/j.ebiom.2022.104265
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发表时间：
2022-10
期刊：
影响因子：
11.1
通讯作者：
Yao, Feng
中科院分区：
文献类型：
--
作者：
Yang, Haitang;Sun, Beibei;Ma, Wenyan;Fan, Liwen;Xu, Ke;Jia, Yunxuan;Xu, Jianlin;Wang, Zhexin;Yao, Feng
关键词：
区域淋巴结(LN)是抗肿瘤免疫的关键器官。矛盾的是，肿瘤引流淋巴结(TDLN)通常是肺癌肿瘤转移的首发部位。肺癌患者TDLN的状态与原发肿瘤床对免疫检查点抑制剂(ICIS)的反应之间的关系在很大程度上是未知的。此外，关于TDLN对ICIS的反应的研究也很少。我们对68例接受新辅助ICIS加手术的肺癌患者的原发肿瘤床和成对TDLN(侵袭性/非侵袭性)的放射学、代谢(18F-FDG)和病理反应进行了表征和比较。此外，我们使用多重免疫荧光技术对TDLN内免疫和非免疫细胞的空间分布进行了研究。分别研究原发肺肿瘤床和配对TDLN的治疗反应(如病理完全(PCR)或主要反应(MPR))。我们观察到，在放射学、代谢(18F-FDG摄取)和病理改变方面，TDLN对ICIS的反应与其配对的原发肺肿瘤明显不同。新辅助ICIS治疗特异性地降低了具有PCR/MPR的原发肿瘤床中18F-FDG反映的代谢活性，但不降低其TDLN对应的代谢活性。此外，在匹配的原发肿瘤床中，侵袭性TDLN的存在与较差的病理反应相关，并预示着治疗后肿瘤的快速复发。空间轮廓显示T细胞在侵袭的TDLN转移灶内被排除在外，并减少了转移灶周围非受累区域的多种免疫和非免疫成分。这些结果提供了第一个临床相关的证据，证明了在ICIS治疗下TDLN的独特反应模式，并揭示了TDLNS状态与其配对的原发肿瘤对ICIS的反应在肺癌中的相关性被低估。本课题得到了国家自然科学基金项目中国(82072570~姚芬芳；82002941~孙宝强)、上海市胸科医院优秀人才计划(TOF)、上海市胸科医院青年基础基金项目(2021YNJCQ2~杨海华)、上海市高水平地方高校创新研究团队(SHSMU-ZLCX20212302~姚芬芳)的资助。
Regional lymph node (LN) acts as a pivotal organ for antitumor immunity. Paradoxically, tumor-draining LNs (TDLNs) are usually the first site of tumor metastasis in lung cancer. It is largely unknown about the association between the status of TDLNs and the response of primary tumor beds to immune checkpoint inhibitors (ICIs) in lung cancer patients. Also, studies characterizing the TDLNs in response to ICIs are scarce. We characterized and compared the radiological, metabolic (18F-FDG) and pathologic responses between primary tumor beds and paired TDLNs (invaded/non-invaded) from 68 lung cancer patients who underwent neoadjuvant ICIs plus surgery. Additionally, we performed the spatial profiling of immune and non-immune cells within TDLNs using multiplexed immunofluorescence. Therapy responses (e.g., pathologic complete (pCR) or major response (MPR)) of primary lung tumor beds and paired TDLNs were investigated separately. We observed that responses of TDLNs to ICIs markedly differ from their paired primary lung tumors regarding the radiological, metabolic (18F-FDG uptake), and pathologic alterations. Neoadjuvant ICIs therapy specifically decreased 18F-FDG-reflected metabolic activity in the primary tumor beds with pCR/MPR but not their TDLNs counterparts. Furthermore, the presence of invaded TDLNs was associated with poor pathologic responses in the matched primary tumor beds and predictive of rapid post-treatment tumor relapse. Spatial profiling demonstrated exclusion of T cell infiltrates within the metastatic lesions of invaded TDLNs, and diminished multiple immune and non-immune compositions in non-involved regions surrounding the metastatic lesions. These results provide the first clinically-relevant evidence demonstrating unique response patterns of TDLNs under ICIs treatment and revealing the underappreciated association of TDLNs status with the response of their paired primary tumors to ICIs in lung cancer. This work was supported by the National Natural Science Foundation of China (82072570 to F. Yao; 82002941 to B. Sun), the excellent talent program of Shanghai Chest Hospital (to F.Y), the Basic Foundation Program for Youth of Shanghai Chest Hospital (2021YNJCQ2 to H.Yang), and the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212302 to F. Yao).
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
利用多功能近红外聚合物点对淋巴结转移进行快速准确的成像
影响因子：
19
作者：
Cao, Fengwen;Guo, Yixiao;Xiong, Liqin
通讯作者：
Xiong, Liqin
DOI：
10.1056/nejmoa1613210
发表时间：
2017-06-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Faries MB;Thompson JF;Cochran AJ;Andtbacka RH;Mozzillo N;Zager JS;Jahkola T;Bowles TL;Testori A;Beitsch PD;Hoekstra HJ;Moncrieff M;Ingvar C;Wouters MWJM;Sabel MS;Levine EA;Agnese D;Henderson M;Dummer R;Rossi CR;Neves RI;Trocha SD;Wright F;Byrd DR;Matter M;Hsueh E;MacKenzie-Ross A;Johnson DB;Terheyden P;Berger AC;Huston TL;Wayne JD;Smithers BM;Neuman HB;Schneebaum S;Gershenwald JE;Ariyan CE;Desai DC;Jacobs L;McMasters KM;Gesierich A;Hersey P;Bines SD;Kane JM;Barth RJ;McKinnon G;Farma JM;Schultz E;Vidal-Sicart S;Hoefer RA;Lewis JM;Scheri R;Kelley MC;Nieweg OE;Noyes RD;Hoon DSB;Wang HJ;Elashoff DA;Elashoff RM
通讯作者：
Elashoff RM
影响因子：
8
作者：
Fransen, Marieke F.;Schoonderwoerd, Mark;Ossendorp, Ferry
通讯作者：
Ossendorp, Ferry
DOI：
10.1073/pnas.1620433114
发表时间：
2017-01-31
影响因子：
11.1
作者：
Chamoto, Kenji;Chowdhury, Partha S.;Honjo, Tasuku
通讯作者：
Honjo, Tasuku