Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.
Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.
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DOI：
10.3390/cancers14010194
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发表时间：
2021-12-31
期刊：
影响因子：
5.2
通讯作者：
Eubank TD
中科院分区：
文献类型：
--
作者：
Pratt HG;Steinberger KJ;Mihalik NE;Ott S;Whalley T;Szomolay B;Boone BA;Eubank TD
胰腺癌患者的生存率非常低。这种令人沮丧的预后部分是由于晚期发现和早期发展的转移，以及胰腺癌的成功治疗也缺乏。一种潜在的治疗方法是免疫疗法，它已成功地应用于几种癌症。尽管在其他癌症类型中取得了成功，但在胰腺癌中进展甚微。为了了解这些缺点，我们探讨了巨噬细胞和中性粒细胞的作用，这两种主要的免疫细胞类型在胰腺肿瘤环境中。在这篇综述中，我们讨论了巨噬细胞和中性粒细胞如何导致胰腺癌特有的恶劣环境。我们进一步探索这些免疫细胞如何影响标准治疗并降低其有效性。巨噬细胞和中性粒细胞最终可能成为改善胰腺癌患者预后的靶点。尽管近年来生存率略有提高，但胰腺癌仍然是一种致命的疾病，5年生存率仅为9%。这些不良结局是由早期检测失败、治疗耐药性和早期转移性扩散倾向造成的。迫切需要发现创新的治疗方法，以靶向使胰腺癌在很大程度上无法治愈的耐药机制。在这篇综述中，我们讨论了胰腺肿瘤的免疫组成，包括违反直觉的事实，即胰腺癌中存在显著的炎症免疫浸润，但抗肿瘤机制被颠覆，免疫行为被抑制。在这里，我们强调免疫细胞相互作用如何产生肿瘤进展和治疗抗性。我们缩小了肿瘤巨噬细胞（TAM）的空间排列，极性/功能，招聘和起源，引入一个概念，与肿瘤中性粒细胞（TAN）的相互作用使微环境永久化。巨噬细胞和中性粒细胞活动的后遗症有助于肿瘤重塑、纤维化、缺氧和进展。我们还讨论了导致对标准护理方式产生抵抗力的免疫机制。最后，我们描述了一个干部的治疗目标，包括那些旨在克服TAM和TAN的招聘和功能，以规避胰腺癌免疫浸润提出的障碍。
The survival rates for patients with pancreatic adenocarcinoma are very low. This dismal prognosis is due in part to late detection and early development of metastases, and successful treatments for pancreatic adenocarcinoma are also lacking. One potential method of treatment is immunotherapy, which has been successfully implemented in several cancers. Despite success in other cancer types, there has been little progress in pancreatic adenocarcinoma. To understand these shortcomings, we explore the roles of macrophages and neutrophils, two prominent immune cell types in the pancreatic tumor environment. In this review, we discuss how macrophages and neutrophils lead to the harsh environment that is unique to pancreatic adenocarcinoma. We further explore how these immune cells can impact standard of care therapies and decrease their effectiveness. Macrophages and neutrophils could ultimately be targeted to improve outcomes for patients with pancreatic adenocarcinoma. Despite modest improvements in survival in recent years, pancreatic adenocarcinoma remains a deadly disease with a 5-year survival rate of only 9%. These poor outcomes are driven by failure of early detection, treatment resistance, and propensity for early metastatic spread. Uncovering innovative therapeutic modalities to target the resistance mechanisms that make pancreatic cancer largely incurable are urgently needed. In this review, we discuss the immune composition of pancreatic tumors, including the counterintuitive fact that there is a significant inflammatory immune infiltrate in pancreatic cancer yet anti-tumor mechanisms are subverted and immune behaviors are suppressed. Here, we emphasize how immune cell interactions generate tumor progression and treatment resistance. We narrow in on tumor macrophage (TAM) spatial arrangement, polarity/function, recruitment, and origin to introduce a concept where interactions with tumor neutrophils (TAN) perpetuate the microenvironment. The sequelae of macrophage and neutrophil activities contributes to tumor remodeling, fibrosis, hypoxia, and progression. We also discuss immune mechanisms driving resistance to standard of care modalities. Finally, we describe a cadre of treatment targets, including those intended to overcome TAM and TAN recruitment and function, to circumvent barriers presented by immune infiltration in pancreatic adenocarcinoma.
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影响因子：
20.3
作者：
Christoffersson, Gustaf;Vagesjo, Evelina;Phillipson, Mia
通讯作者：
Phillipson, Mia
DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
胰腺导管腺癌条件培养基诱导的肿瘤驱动类巨噬细胞通过分泌IL-8促进肿瘤转移
影响因子：
4
作者：
Chen SJ;Lian GD;Li JJ;Zhang QB;Zeng LJ;Yang KG;Huang CM;Li YQ;Chen YT;Huang KH
通讯作者：
Huang KH
影响因子：
8.8
作者：
Candido JB;Morton JP;Bailey P;Campbell AD;Karim SA;Jamieson T;Lapienyte L;Gopinathan A;Clark W;McGhee EJ;Wang J;Escorcio-Correia M;Zollinger R;Roshani R;Drew L;Rishi L;Arkell R;Evans TRJ;Nixon C;Jodrell DI;Wilkinson RW;Biankin AV;Barry ST;Balkwill FR;Sansom OJ
通讯作者：
Sansom OJ
DOI：
10.1152/ajpregu.00320.2011
发表时间：
2012-05-01
影响因子：
2.8
作者：
Benson, Douglas D.;Meng, Xianzhong;Barnett, Carlton C., Jr.
通讯作者：
Barnett, Carlton C., Jr.