Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer.
Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer.
复制标题
肿瘤相关巨噬细胞与III期结直肠癌复发风险
DOI：
10.1002/cjp2.267
复制
发表时间：
2022-07
影响因子：
4.1
通讯作者：
Laghi, Luigi
中科院分区：
文献类型：
--
作者：
Cavalleri, Tommaso;Greco, Luana;Rubbino, Federica;Hamada, Tsuyoshi;Quaranta, Maria;Grizzi, Fabio;Sauta, Elisabetta;Craviotto, Vincenzo;Bossi, Paola;Vetrano, Stefania;Rimassa, Lorenza;Torri, Valter;Bellazzi, Riccardo;Mantovani, Alberto;Ogino, Shuji;Malesci, Alberto;Laghi, Luigi
关键词：
肿瘤相关巨噬细胞（TAM）对结直肠癌（CRC）的预后具有独特的有利影响，尽管它们与阶段特异性结局的关系尚不清楚。我们评估了236例患者（其中165例接受了术后FOLFOX治疗）切除的III期CRC浸润前沿的CD 68+和CD 163 + TAM密度及其与无病生存期（DFS）的关系。在来自癌症基因组图谱（TCGA）的59例III期CRC和FOLFOX治疗患者中，通过计算机模拟研究了巨噬细胞mRNA与临床结局之间的相关性。在共培养模型中检测了SW 480和HT 29细胞以及巨噬细胞与FOLFOX的生物学相互作用。在接受FOLFOX治疗的患者中，低TAM密度与较短的DFS相关（CD 68+，p = 0.0001; CD 163+，p = 0.0008），但在未接受治疗的患者中则不相关。通过多变量考克斯分析，只有低TAM（CD 68+，p = 0.001; CD 163+，p = 0.002）和淋巴结状态（CD 68+，p = 0.009; CD 163+，p = 0.007）保持独立的预测值。在TCGA队列中，高CD 68 mRNA水平与更好的结局相关（p = 0.02）。巨噬细胞增强了FOLFOX对CRC细胞的细胞毒性（p < 0.01），药物将巨噬细胞从M2-表型极化为M1-表型。低TAM密度识别辅助治疗后复发风险较高的III期CRC患者，巨噬细胞可以增加微转移的化疗敏感性。
Tumor‐associated macrophages (TAMs) have a unique favorable effect on the prognosis of colorectal cancer (CRC), although their association with stage‐specific outcomes remains unclear. We assessed the densities of CD68+ and CD163+ TAMs at the invasive front of resected CRC stage III CRC from 236 patients, 165 of whom received post‐surgical FOLFOX treatment, and their relationship with disease‐free survival (DFS). Associations between macrophage mRNAs and clinical outcome were investigated in silico in 59 stage III CRC and FOLFOX‐treated patients from The Cancer Genome Atlas (TCGA). Biological interactions of SW480 and HT29 cells and macrophages with FOLFOX were tested in co‐culture models. Low TAM densities were associated with shorter DFS among patients receiving FOLFOX (CD68+, p = 0.0001; CD163+, p = 0.0008) but not among those who were untreated. By multivariate Cox analysis, only low TAM (CD68+, p = 0.001; CD163+, p = 0.002) and nodal status (CD68+, p = 0.009; CD163+, p = 0.007) maintained an independent predictive value. In the TCGA cohort, high CD68 mRNA levels were associated with better outcome (p = 0.02). Macrophages enhanced FOLFOX cytotoxicity on CRC cells (p < 0.01), and drugs oriented macrophage polarization from M2‐ to M1‐phenotype. Low TAM densities identify stage III CRC patients at higher risk of recurrence after adjuvant therapy, and macrophages can augment the chemo‐sensitivity of micro‐metastases.
登录
查看更多内容
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
DOI：
10.1158/1078-0432.ccr-12-0605
发表时间：
2012-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gavin PG;Colangelo LH;Fumagalli D;Tanaka N;Remillard MY;Yothers G;Kim C;Taniyama Y;Kim SI;Choi HJ;Blackmon NL;Lipchik C;Petrelli NJ;O'Connell MJ;Wolmark N;Paik S;Pogue-Geile KL
通讯作者：
Pogue-Geile KL
DOI：
10.1056/nejmoa1713709
发表时间：
2018-03-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grothey A;Sobrero AF;Shields AF;Yoshino T;Paul J;Taieb J;Souglakos J;Shi Q;Kerr R;Labianca R;Meyerhardt JA;Vernerey D;Yamanaka T;Boukovinas I;Meyers JP;Renfro LA;Niedzwiecki D;Watanabe T;Torri V;Saunders M;Sargent DJ;Andre T;Iveson T
通讯作者：
Iveson T
影响因子：
28.4
作者：
Tie, Jeanne;Cohen, Joshua D.;Gibbs, Peter
通讯作者：
Gibbs, Peter