Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome.
Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome.
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DOI：
10.1007/s00109-023-02324-5
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发表时间：
2023-07
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目前迫切需要确定预测结直肠癌（CRC）免疫原性的因素。粘液性结直肠癌是结直肠癌的一种独特的组织学亚型，与对化疗的不良反应相关。最近的证据表明，肠道兼性厌氧菌梭杆菌可能在粘液性CRC中特别普遍。本研究的目的是评估粘液性结直肠癌中梭杆菌丰度与免疫细胞组成和预后的关系。我们的研究包括两个独立的结直肠癌患者队列，癌症基因组图谱（TCGA）队列和来自博蒙RCSI癌症中心（BRCC）的直肠癌队列。使用Cell DIVE技术对来自BRCC队列的肿瘤微阵列（TMA）进行多重免疫荧光染色。我们的队列包括87例（13.3%）粘液性CRC和565例（86.7%）非粘液性CRC。TCGA数据集中的粘液性CRC与CD 8+淋巴细胞（p = 0.018）、调节性T细胞（p = 0.001）和M2巨噬细胞（p = 0.001）的比例增加相关。在BRCC队列中，粘液性RC与CD 8+淋巴细胞（p = 0.022）、调节性T细胞（p = 0.047）和B细胞（p = 0.025）计数增加相关。高梭杆菌丰度与CD 4+淋巴细胞（p = 0.031）和M1巨噬细胞（p = 0.006）比例增加相关，而M2巨噬细胞（p = 0.043）在该队列中代表性不足。在我们的粘液性CRC TCGA队列中梭杆菌相对丰度增加的患者倾向于具有更好的临床结局（DSS：似然比p = 0.04，对数秩p = 0.052）。梭杆菌丰度可能与粘液性结直肠癌的预后改善相关，这可能是由于对宿主免疫应答的调节作用。·未发现增加的梭杆菌相对丰度与粘液性CRC中的微卫星不稳定性相关。·增加的梭杆菌相对丰度与M2/M1巨噬细胞转换相关，这在M2巨噬细胞过表达的粘液性CRC中尤其显著。·增加的梭杆菌相对丰度与粘液性CRC中疾病特异性存活的显著改善相关。·我们的研究结果在我们自己的内部粘液性和非粘液性直肠癌队列中的蛋白质水平上得到了验证。在线版本包含补充材料，可通过10.1007/s 00109 -023-02324-5获得。
There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the association of Fusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proportion of CD8 + lymphocytes (p = 0.018), regulatory T-cells (p = 0.001) and M2 macrophages (p = 0.001). In the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. High Fusobacterium abundance was associated with an increased proportion of CD4 + lymphocytes (p = 0.031) and M1 macrophages (p = 0.006), whilst M2 macrophages (p = 0.043) were under-represented in this cohort. Patients with increased Fusobacterium relative abundance in our mucinous CRC TCGA cohort tended to have better clinical outcomes (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance may be associated with improved outcomes in mucinous CRC, possibly due to a modulatory effect on the host immune response. • Increased Fusobacterium relative abundance was not found to be associated with microsatellite instability in mucinous CRC. • Increased Fusobacterium relative abundance was associated with an M2/M1 macrophage switch, which is especially significant in mucinous CRC, where M2 macrophages are overexpressed. • Increased Fusobacterium relative abundance was associated with a significant improvement in disease specific survival in mucinous CRC. • Our findings were validated at a protein level within our own in house mucinous and non-mucinous rectal cancer cohorts. The online version contains supplementary material available at 10.1007/s00109-023-02324-5.
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DOI：
10.1056/nejmoa2201445
发表时间：
2022-06-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
7.3
作者：
Pan Y;Yu Y;Wang X;Zhang T
通讯作者：
Zhang T
影响因子：
12.4
作者：
Lindner AU;Salvucci M;McDonough E;Cho S;Stachtea X;O'Connell EP;Corwin AD;Santamaria-Pang A;Carberry S;Fichtner M;Van Schaeybroeck S;Laurent-Puig P;Burke JP;McNamara DA;Lawler M;Sood A;Graf JF;Rehm M;Dunne PD;Longley DB;Ginty F;Prehn JHM
通讯作者：
Prehn JHM
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
影响因子：
4.7
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
通讯作者：
Yang W
影响因子：
24.5
作者：
Salvucci, Manuela;Crawford, Nyree;Stott, Katie;Bullman, Susan;Longley, Daniel B.;Prehn, Jochen H. M.
通讯作者：
Prehn, Jochen H. M.