Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC.
Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC.
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DOI：
10.1016/j.jtho.2020.09.027
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Gibbons DL
中科院分区：
文献类型：
--
作者：
Gaudreau PO;Negrao MV;Mitchell KG;Reuben A;Corsini EM;Li J;Karpinets TV;Wang Q;Diao L;Wang J;Federico L;Parra-Cuentas ER;Khairullah R;Behrens C;Correa AM;Gomez D;Little L;Gumbs C;Kadara HN;Fujimoto J;McGrail DJ;Vaporciyan AA;Swisher SG;Walsh G;Antonoff MB;Weissferdt A;Tran H;Roarty E;Haymaker C;Bernatchez C;Zhang J;Futreal PA;Wistuba II;Cascone T;Heymach JV;Sepesi B;Zhang J;Gibbons DL
PD-1/PD-L1免疫检查点阻断（ICB）和化疗的组合彻底改变了晚期非小细胞肺癌（NSCLC）的治疗，但这种协同作用的机制仍不完全清楚。在这项研究中，我们探讨了新辅助化疗和可切除的非小细胞肺癌（NSCLC）的免疫微环境（IME）之间的关系，以确定化疗可能增强ICB效果的新机制。比较了511例接受新辅助化疗后手术（NCT）与前期手术（US）治疗的患者的基因组、转录组和免疫谱数据，以确定来自全外显子组测序的IME的差异特征。（NCT=18; US=73），RNA微阵列（NCT=45; US=202），流式细胞术（NCT=17; US=39）、多重免疫荧光（NCT=10; US=72）、T细胞受体（TCR）测序（NCT=16和US=63）和循环细胞因子（NCT=18; US=73）。NCT与细胞毒性CD 8 + T细胞和CD 20 + B细胞浸润增加相关。此外，NCT与CD 8 + CD 103+和CD 4 + CD 103 +PD-1+ TIM 3 −组织驻留记忆T细胞的增加相关。基因表达谱支持CD 8+和CD 4 + T细胞的记忆功能。然而，NCT不影响TCR克隆性、丰富性或肿瘤突变负荷。最后，NCT与基线和术后第4周血浆BDNF（TrkB）降低相关。我们的研究支持，在可切除NSCLC的背景下，新辅助化疗通过IME中的T和B细胞募集以及通过细胞毒性和记忆性CD 8+和CD 4+记忆辅助T细胞的表型变化来促进抗肿瘤免疫。
The combination of PD-1/PD-L1 immune checkpoint blockade (ICB) and chemotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable non-small cell lung cancer (NSCLC) in order to identify novel mechanisms by which chemotherapy may enhance the effect of ICB. Genomic, transcriptomic and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) vs upfront surgery (US) were compared to determine differential characteristics of the IMEs derived from whole exome sequencing (NCT=18; US=73), RNA microarray (NCT=45; US=202), flow cytometry (NCT=17; US=39), multiplex immunofluorescence (NCT=10; US=72), T cell receptor (TCR) sequencing (NCT=16 and US=63) and circulating cytokines (NCT=18; US=73). NCT was associated with increased infiltration of cytotoxic CD8+ T cells and CD20+ B cells. Moreover, NCT was associated with increases in CD8+CD103+ and CD4+CD103+PD-1+TIM3− tissue resident memory T cells. Gene expression profiling supported memory function of CD8+ and CD4+ T cells. However, NCT did not impact TCR clonality, richness or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 post-surgery. Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes anti-tumor immunity through T and B cell recruitment in the IME, and through a phenotypic change towards cytotoxic and memory CD8+ and CD4+ memory helper T cells.
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DOI：
10.1097/cji.0b013e3181b56af4
发表时间：
2010-01
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Liu P;Jaffar J;Hellstrom I;Hellstrom KE
通讯作者：
Hellstrom KE
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：
4.4
作者：
Djenidi, Faycal;Adam, Julien;Mami-Chouaib, Fathia
通讯作者：
Mami-Chouaib, Fathia
影响因子：
45.3
作者：
Pignon, Jean-Pierre;Tribodet, Helene;Le Chevalier, Thierry
通讯作者：
Le Chevalier, Thierry
影响因子：
3.9
作者：
Kim, Jee-Eun;Jang, Min-Ja;Kim, Daejin
通讯作者：
Kim, Daejin