Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer.
Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer.
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进展期胃癌恶性腹水中促癌巨噬细胞占优势。
DOI：
10.1038/s12276-020-00538-y
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发表时间：
2020-12
影响因子：
12.8
通讯作者：
Park WY
中科院分区：
文献类型：
--
作者：
Eum HH;Kwon M;Ryu D;Jo A;Chung W;Kim N;Hong Y;Son DS;Kim ST;Lee J;Lee HO;Park WY
由于腹膜转移，随着疾病的发展，胃癌患者会出现恶性腹水。伴有恶性腹水的GC患者在恶性腹水发作后有一个迅速恶化的临床病程和较短的生存期。需要为这一亚群患者更好地优化治疗策略。为了明确GC恶性腹水的细胞特征，我们用单细胞RNA测序技术对4例恶性腹水和1例脑脊液中的肿瘤细胞和肿瘤相关巨噬细胞(TAMs)进行了鉴定。通过健康血源性单核细胞的体外分化产生M1和M2巨噬细胞的参考转录本，并用于评估TAMS的炎症特性。我们分析了180个细胞，包括肿瘤细胞、巨噬细胞和间皮细胞。肿瘤促进信号的动态交换，包括CCL3-CCR1或IL1B-IL1R2的相互作用，提示肿瘤细胞的巨噬细胞募集和抗炎调节。通过将这些数据与M1型和M2型巨噬细胞的参考转录本进行比较，我们发现从GC恶性腹水中恢复的巨噬细胞具有非炎性特征。使用公开的数据集，我们证明了单细胞转录组驱动的M2特异性信号与GC预后不良相关。我们的数据表明，TAMS的抗炎特性受肿瘤细胞控制，并为GC患者的治疗策略提供了启示，在这些治疗策略中，针对癌细胞和巨噬细胞的联合治疗可能具有互惠的协同效应。对名为巨噬细胞的白细胞和积聚在腹部的恶性腹水中的肿瘤细胞之间的相互作用的洞察，可能会产生治疗晚期胃癌的新策略。韩国首尔的研究人员由韩国天主教大学的李海克和三星医疗中心的朴勇洋领导，他们将健康人的巨噬细胞与胃癌腹水的巨噬细胞进行了比较。他们确定了肿瘤细胞和巨噬细胞之间的分子信号相互作用，这种相互作用将巨噬细胞招募到腹水中，并将它们转化为更多的抗炎形式。然后，巨噬细胞能够促进癌细胞的活动。结果表明，能够抑制或耗尽蛋白质的化学物质现在被发现参与控制这些协同作用，可能成为一类新的治疗剂。
Gastric cancer (GC) patients develop malignant ascites as the disease progresses owing to peritoneal metastasis. GC patients with malignant ascites have a rapidly deteriorating clinical course with short survival following the onset of malignant ascites. Better optimized treatment strategies for this subset of patients are needed. To define the cellular characteristics of malignant ascites of GC, we used single-cell RNA sequencing to characterize tumor cells and tumor-associated macrophages (TAMs) from four samples of malignant ascites and one sample of cerebrospinal fluid. Reference transcriptomes for M1 and M2 macrophages were generated by in vitro differentiation of healthy blood-derived monocytes and applied to assess the inflammatory properties of TAMs. We analyzed 180 cells, including tumor cells, macrophages, and mesothelial cells. Dynamic exchange of tumor-promoting signals, including the CCL3–CCR1 or IL1B–IL1R2 interactions, suggests macrophage recruitment and anti-inflammatory tuning by tumor cells. By comparing these data with reference transcriptomes for M1-type and M2-type macrophages, we found noninflammatory characteristics in macrophages recovered from the malignant ascites of GC. Using public datasets, we demonstrated that the single-cell transcriptome-driven M2-specific signature was associated with poor prognosis in GC. Our data indicate that the anti-inflammatory characteristics of TAMs are controlled by tumor cells and present implications for treatment strategies for GC patients in which combination treatment targeting cancer cells and macrophages may have a reciprocal synergistic effect. New strategies for treating advanced gastric cancer could emerge from insights into the interactions between white blood cells called macrophages and tumor cells in fluid known as malignant ascites that accumulates in the abdomen. Researchers in Seoul, South Korea, led by Hae-Ock Lee at The Catholic University of Korea and Woong-Yang Park at the Samsung Medical Center compared macrophages from healthy subjects with those from gastric cancer ascites. They identified molecular signaling interactions between tumor cells and macrophages that recruited macrophages into the ascites and converted them into more anti-inflammatory forms. The macrophages were then able to promote the activities of the cancer cells. The results suggest that chemicals able to inhibit or deplete proteins now identified as involved in controlling these synergistic interactions could become a new class of therapeutic agents.
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影响因子：
--
作者：
Lee J;Cristescu R;Kim KM;Kim K;Kim ST;Park SH;Kang WK
通讯作者：
Kang WK
影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya
影响因子：
64.5
作者：
Azizi E;Carr AJ;Plitas G;Cornish AE;Konopacki C;Prabhakaran S;Nainys J;Wu K;Kiseliovas V;Setty M;Choi K;Fromme RM;Dao P;McKenney PT;Wasti RC;Kadaveru K;Mazutis L;Rudensky AY;Pe'er D
通讯作者：
Pe'er D
影响因子：
82.9
作者：
Cristescu, Razvan;Lee, Jeeyun;Aggarwal, Amit
通讯作者：
Aggarwal, Amit
影响因子：
30.8
作者：
Li, Huipeng;Courtois, Elise T.;Prabhakar, Shyam
通讯作者：
Prabhakar, Shyam