The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy.
The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy.
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DOI：
10.1126/scitranslmed.aan3464
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发表时间：
2018-04-11
影响因子：
17.1
通讯作者：
Weinberg RA
中科院分区：
文献类型：
--
作者：
Krall JA;Reinhardt F;Mercury OA;Pattabiraman DR;Brooks MW;Dougan M;Lambert AW;Bierie B;Ploegh HL;Dougan SK;Weinberg RA
接受手术切除原发性乳腺肿瘤的患者面临转移性复发的风险，该风险在手术后12至18个月急剧上升。乳腺癌早期转移复发的原因长期以来一直存在争议，许多人将这些复发归因于疾病的自然进展。其他人提出，手术切除肿瘤的某些方面触发了原本休眠的转移瘤的生长，导致复发的同步模式。临床数据无法区分这些假设，以前的实验方法也没有提供明确的答案。这种不确定性阻碍了可能减少早期转移复发的治疗方法的开发和应用。我们描述了一个实验模型系统，明确连接手术和随后的伤口愈合反应的肿瘤细胞在远处的解剖部位的产物。具体来说，我们发现手术后诱导的全身炎症反应促进了肿瘤的出现，否则肿瘤的生长受到肿瘤特异性T细胞反应的限制。此外，我们证明，围手术期抗炎治疗显着减少肿瘤生长在这个模型中，这表明类似的方法可能会大大减少乳腺癌患者的早期转移复发。
Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others have proposed that some aspect of surgical tumor resection triggers the outgrowth of otherwise-dormant metastases, leading to the synchronous pattern of relapse. Clinical data cannot distinguish between these hypotheses, and previous experimental approaches have not provided clear answers. Such uncertainty hinders the development and application of therapeutic approaches that could potentially reduce early metastatic relapse. We describe an experimental model system that definitively links surgery and the subsequent wound-healing response to the outgrowth of tumor cells at distant anatomical sites. Specifically, we find that the systemic inflammatory response induced after surgery promotes the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response. Furthermore, we demonstrate that perioperative anti-inflammatory treatment markedly reduces tumor outgrowth in this model, suggesting that similar approaches might substantially reduce early metastatic recurrence in breast cancer patients.
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影响因子：
7.2
作者：
Coussens, Lisa M.;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
影响因子：
3.8
作者：
Cheng, Lee;Swartz, Michael D.;Giordano, Sharon H.
通讯作者：
Giordano, Sharon H.
影响因子：
15.9
作者：
Eyles, Jo;Puaux, Anne-Laure;Abastado, Jean-Pierre
通讯作者：
Abastado, Jean-Pierre
DOI：
10.1073/pnas.1113744109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Cortez-Retamozo, Virna;Etzrodt, Martin;Pittet, Mikael J.
通讯作者：
Pittet, Mikael J.
影响因子：
28.2
作者：
Castaño Z;Marsh T;Tadipatri R;Kuznetsov HS;Al-Shahrour F;Paktinat M;Greene-Colozzi A;Nilsson B;Richardson AL;McAllister SS
通讯作者：
McAllister SS