摘要
胰腺癌是恶性程度最高的消化道肿瘤,5年生存率低于5%,被称为新的“癌中之王”.早期转移是导致胰腺癌预后差的关键因素.微环境在胰腺癌的侵袭转移中发挥重要作用,肿瘤相关成纤维细胞(CAFs)、淋巴细胞、肿瘤相关巨噬细胞(TAMs)等免疫细胞是微环境的重要组成部分.既往研究认为,CAFs可提高胰腺癌的化疗耐药性,促进肿瘤转移.但临床研究发现,通过Hedgehog抑制剂清除CAFs可导致胰腺癌细胞转移增加,患者生存期显著缩短.进一步的机制研究发现,CAFs异质性很高,存在“限癌”及“促癌”等不同亚型,一味剔除间质可能误伤“限癌”CAFs.靶向CAFs特定促癌通路可能是更好的治疗选择.另外,胰腺癌间质中普遍存在CD8+T淋巴细胞毒性降低、TAMs浸润数量增加等特点,且与患者预后密切相关.本文拟就胰腺癌微环境中CAFs及免疫细胞对肿瘤转移能力的影响做一综述,希望进一步提高胰腺转移癌的诊治水平.
Pancreatic cancer is the most malignant gastrointestinal tumor,with a 5-year survival rate of less than 5%,known as the"King of the cancer".Early metastasis is a key factor leading to poor prognosis in pancreatic cancer.Micro-environment plays an important role in promoting invasion and metastasis of pancreatic cancer.Cancer-associated fibroblasts(CAFs),lymphocytes and tumorassociated macrophages(TAM),are important components of the micro-environment.Previous studies suggested that CAFs may improve chemo-resistance and promote tumor metastasis of pancreatic cancer cells,Nonetheless,clinical trials showed that clearance of CAFs by Hedgehog inhibitors leads to increased metastasis of pancreatic cancer cells and a significant reduction in patient survival.Further mechanism research found that CAFs are highly heterogeneous,and there are different subtypes,such as"limiting cancer"and"promoting cancer"CAFs.It is possible that the general deletion may damage the"cancer-limited"CAFs,and targeted therapy against cancer-promoting pathways in CAFs may become better treatment options.Pancreatic cancer stroma is generally characterized by low toxicity of CD8+T lymphocytes and increased TAM infiltration,which are closely associated with the prognosis of patients.This review summarized the effects of CAFs and immune cells on tumor metastasis in pancreatic cancer micro-environment,and hopefully to improve the diagnosis and treatment of pancreatic cancer.
作者
孔祥毓
朱建伟
李兆申
Kong Xiangyu;Zhu Jianwei;Li Zhaoshen(Department of Gastroenterology,Changhai Hospital Affiliated to Naval Military Medical University,Shanghai 200438,China)
出处
《中华转移性肿瘤杂志》
2018年第3期1-6,共6页
Chinese Journal of Metastatic Cancer
基金
国家自然科学基金(81772640)
关键词
胰腺癌
微环境
转移性
肿瘤相关成纤维细胞
免疫细胞
Pancreatic cancer
Microenvironment
Metastasis
Cancer-associated fibroblast
Immune cells
