Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving operative paclitaxel plus platinum chemotherapy.
Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving operative paclitaxel plus platinum chemotherapy.
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DOI：
10.1038/s41389-021-00359-2
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发表时间：
2021-10-26
期刊：
影响因子：
6.2
通讯作者：
Tan L
中科院分区：
文献类型：
--
作者：
Chen Z;Huang Y;Hu Z;Zhao M;Bian Y;Chen Z;Zheng Y;Bi G;Pang Y;Zhan C;Lin Z;Guo W;Wang Q;Tan L
食管鳞状细胞癌（ESCC）占全世界食管癌病例的90%。虽然新辅助化疗（NACT-ESCC）提高了ESCC患者的生存率，但这些患者的五年生存率令人沮丧。肿瘤微环境（TME）和肿瘤异质性降低了ESCC治疗的疗效。在我们的研究中，从5名单独接受手术的ESCC患者（SA-ESCC）和5名接受术前紫杉醇加铂化疗（NACT-ESCC）的患者中获得的113，581个细胞用于scRNA-seq分析，以探索分子和细胞重编程模式。结果显示，NACT-ESCC患者的样本表现出不同于SA-ESCC患者的恶性细胞和TME的特征。来自NACT-ESCC样品的癌细胞主要处于“中间瞬时阶段”。基质细胞动力学显示分子和功能的转变，形成免疫激活微环境。APOE、APOC 1和SPP 1在肿瘤相关巨噬细胞中高度表达，导致抗炎巨噬细胞表型。SA-ESCC和NACT-ESCC组织中的CD 8 + T细胞水平存在显著差异。免疫检查点分析显示LAG 3是NACT-ESCC和SA-ESCC患者的潜在免疫靶点。细胞间相互作用分析表明，TME中存在复杂的细胞间通讯网络。总之，我们的研究结果阐明了NACT-ESCC和ESCC患者的分子和细胞重编程。这些发现为ESCC患者的潜在诊断和治疗靶点提供了信息。
Esophageal squamous cell carcinoma (ESCC) accounts for 90% of all cases of esophageal cancers worldwide. Although neoadjuvant chemotherapy (NACT-ESCC) improves the survival of ESCC patients, the five-year survival rate of these patients is dismal. The tumor microenvironment (TME) and tumor heterogeneity decrease the efficacy of ESCC therapy. In our study, 113,581 cells obtained from five ESCC patients who underwent surgery alone (SA-ESCC) and five patients who underwent preoperative paclitaxel plus platinum chemotherapy (NACT-ESCC), were used for scRNA-seq analysis to explore molecular and cellular reprogramming patterns. The results showed samples from NACT-ESCC patients exhibited the characteristics of malignant cells and TME unlike samples from SA-ESCC patients. Cancer cells from NACT-ESCC samples were mainly at the ‘intermediate transient stage’. Stromal cell dynamics showed molecular and functional shifts that formed the immune-activation microenvironment. APOE, APOC1, and SPP1 were highly expressed in tumor-associated macrophages resulting in anti-inflammatory macrophage phenotypes. Levels of CD8+ T cells between SA-ESCC and NACT-ESCC tissues were significantly different. Immune checkpoints analysis revealed that LAG3 is a potential immunotherapeutic target for both NACT-ESCC and SA-ESCC patients. Cell–cell interactions analysis showed the complex cell-cell communication networks in the TME. In summary, our findings elucidate on the molecular and cellular reprogramming of NACT-ESCC and ESCC patients. These findings provide information on the potential diagnostic and therapeutic targets for ESCC patients.
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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
CD33在造血干细胞中的遗传失活，使CAR T细胞免疫疗法患有急性髓样白血病。
影响因子：
64.5
作者：
Kim MY;Yu KR;Kenderian SS;Ruella M;Chen S;Shin TH;Aljanahi AA;Schreeder D;Klichinsky M;Shestova O;Kozlowski MS;Cummins KD;Shan X;Shestov M;Bagg A;Morrissette JJD;Sekhri P;Lazzarotto CR;Calvo KR;Kuhns DB;Donahue RE;Behbehani GK;Tsai SQ;Dunbar CE;Gill S
通讯作者：
Gill S
影响因子：
7.3
作者：
Leduc C;Adam J;Louvet E;Sourisseau T;Dorvault N;Bernard M;Maingot E;Faivre L;Cassin-Kuo MS;Boissier E;Dessoliers MC;Robin A;Casiraghi O;Even C;Temam S;Olaussen KA;Soria JC;Postel-Vinay S
通讯作者：
Postel-Vinay S
影响因子：
3.8
作者：
Koenig, Lisa;Mairinger, Fabian D.;Bankfalvi, Agnes
通讯作者：
Bankfalvi, Agnes
影响因子：
2.4
作者：
Lin, Dong;Liu, Guobing;Tan, Lijie
通讯作者：
Tan, Lijie