Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4(+) T Cells in the Central Region of pMMR CRC.
Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4(+) T Cells in the Central Region of pMMR CRC.
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免疫景观分析揭示 pMMR CRC 中央区域细胞毒性 CD4( ) T 细胞的预后意义
DOI：
10.3389/fonc.2021.724232
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Qi J;Liu X;Yan P;He S;Lin Y;Huang Z;Zhang S;Xie S;Li Y;Lu X;Wu Y;Zhou Y;Yuan J;Cai T;Zheng X;Ding Y;Yang W
错配修复正常的结直肠癌（pMMR CRC）缺乏有效的治疗方法，预后较差，这可归因于肿瘤微环境的复杂性。免疫细胞的协同功能对抗肿瘤免疫至关重要。然而，pMMR CRC免疫微环境中免疫细胞的空间特征及其与临床预后的关系尚未完全了解。同时，作为pMMR CRC一线治疗方法的新辅助化疗（NCT）的免疫调节作用需要进一步研究。因此，本研究旨在探讨免疫细胞的空间动态及其在pMMR CRC中的预后价值。
我们分析了从77例II/III期pMMR CRC患者（包括39例未接受NCT治疗和38例接受NCT治疗的患者）收集的福尔马林固定、石蜡包埋的肿瘤组织中的各种免疫细胞。我们使用优化的多重免疫组织化学（mIHC）来识别和量化pMMR CRC中免疫细胞的密度、类型和位置。进行多变量生存分析以评估pMMR CRC患者的免疫特征与临床预后的关系。
大多数T细胞亚群、B细胞和巨噬细胞在pMMR CRC中心区域的密度高于浸润边缘。肿瘤浸润淋巴细胞（TILs），特别是肿瘤中心区域CD4 + GzmB + T细胞的浸润被确定与患者的预后呈正相关。多变量分析证实，CD4 + GzmB + T细胞群是非NCT组无病生存期（DFS）的独立预测因子。同时，NCT增强了pMMR CRC中心区域CD4 + GzmB + T细胞的浸润，这也被确定为NCT组总生存期（OS）和DFS的独立保护因素。
我们证明位于肿瘤中心的CD4 + GzmB + T细胞水平可为pMMR CRC患者提供重要的预后价值。并且新辅助化疗的应用进一步提高了CD4 + GzmB + T细胞在中心区域的浸润。需要进一步研究CD4 + GzmB + T细胞在肿瘤免疫治疗中的应用。
Mismatch repair proficient colorectal cancer (pMMR CRC) lacks effective treatments and has a poor prognosis, which can be attributed to the complexity of tumor microenvironment. The coordinated function of immune cells is vital to anti-tumor immunity. However, the spatial characteristics of immune cells in the pMMR CRC immune microenvironment and their relationship with clinical prognosis are not fully understood. Meanwhile, the immune modulatory effect of neoadjuvant chemotherapy (NCT), which is the first-line treatment of pMMR CRC, needs further investigation. Therefore, this study aims to explore the spatial dynamics of immune cells and its prognostic value in pMMR CRC. We analyzed the various immune cells in formalin-fixed, paraffin-embedded tumor tissues which were collected from 77 patients with stage II/III of pMMR CRC, including 39 non-NCT treated and 38 NCT treated patients. We used the optimized multiplex immunohistochemistry (mIHC) to identify and quantify the density, type and location of immune cells in pMMR CRC. Multivariate survival analysis was performed to assess the relationship of immune profiles and clinical prognosis of pMMR CRC patients. The densities of most T cell subsets, B cells and macrophages were higher in the central region of the pMMR CRC than in the invasion margin. Tumor infiltrating lymphocytes (TILs), especially the infiltration of CD4+ GzmB+ T cells in the central region of the tumor was identified to be positively correlated with the prognosis of the patients. Multivariate analysis confirmed that CD4+ GzmB+ T cells population was an independent predictor of disease-free survival (DFS) in non-NCT group. Meanwhile, NCT enhanced the infiltration of CD4+ GzmB+ T cells in the central region of the pMMR CRC, which was also identified as an independent protective factor of overall survival (OS) and DFS in NCT group. We demonstrated that the level of CD4+ GzmB+ T cells located in the center of tumor could provide great prognostic value for pMMR CRC patients. And the application of neoadjuvant chemotherapy further improves the infiltration of CD4+ GzmB+ T cells in the central compartment. Further studies into the application of CD4+ GzmB+ T cells in tumor immunotherapy are needed.
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影响因子：
7.4
作者：
Galon J;Pagès F;Marincola FM;Angell HK;Thurin M;Lugli A;Zlobec I;Berger A;Bifulco C;Botti G;Tatangelo F;Britten CM;Kreiter S;Chouchane L;Delrio P;Arndt H;Asslaber M;Maio M;Masucci GV;Mihm M;Vidal-Vanaclocha F;Allison JP;Gnjatic S;Hakansson L;Huber C;Singh-Jasuja H;Ottensmeier C;Zwierzina H;Laghi L;Grizzi F;Ohashi PS;Shaw PA;Clarke BA;Wouters BG;Kawakami Y;Hazama S;Okuno K;Wang E;O'Donnell-Tormey J;Lagorce C;Pawelec G;Nishimura MI;Hawkins R;Lapointe R;Lundqvist A;Khleif SN;Ogino S;Gibbs P;Waring P;Sato N;Torigoe T;Itoh K;Patel PS;Shukla SN;Palmqvist R;Nagtegaal ID;Wang Y;D'Arrigo C;Kopetz S;Sinicrope FA;Trinchieri G;Gajewski TF;Ascierto PA;Fox BA
通讯作者：
Fox BA
DOI：
10.6004/jnccn.2018.0061
发表时间：
2018-07
期刊：
Journal of the National Comprehensive Cancer Network : JNCCN
影响因子：
--
作者：
Benson AB;Venook AP;Al-Hawary MM;Cederquist L;Chen YJ;Ciombor KK;Cohen S;Cooper HS;Deming D;Engstrom PF;Grem JL;Grothey A;Hochster HS;Hoffe S;Hunt S;Kamel A;Kirilcuk N;Krishnamurthi S;Messersmith WA;Meyerhardt J;Mulcahy MF;Murphy JD;Nurkin S;Saltz L;Sharma S;Shibata D;Skibber JM;Sofocleous CT;Stoffel EM;Stotsky-Himelfarb E;Willett CG;Wuthrick E;Gregory KM;Gurski L;Freedman-Cass DA
通讯作者：
Freedman-Cass DA
DOI：
10.1016/j.jtho.2020.09.027
发表时间：
2021-01
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
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
通讯作者：
Gibbons DL
影响因子：
16.6
作者：
Desbois M;Udyavar AR;Ryner L;Kozlowski C;Guan Y;Dürrbaum M;Lu S;Fortin JP;Koeppen H;Ziai J;Chang CW;Keerthivasan S;Plante M;Bourgon R;Bais C;Hegde P;Daemen A;Turley S;Wang Y
通讯作者：
Wang Y
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