微生物群对胰腺癌免疫治疗影响的研究现状

doi:10.3877/cma.j.issn.1674-0793.2022.06.003

即使是早期的胰腺癌，通常被认为可以通过手术切除治疗的患者5年生存率也只有25%^[1]。免疫治疗已逐渐成为治疗胰腺癌的新策略^[2]。肿瘤微环境是一个包含巨噬细胞、肥大细胞、嗜中性粒细胞、骨髓来源抑制性细胞（myeloid-derived suppressor cells，MDSCs）、树突状细胞、自然杀伤细胞、适应性免疫细胞以及间质等成分的复杂微小空间，消化道微生物群也是胰腺肿瘤微环境的重要组成部分^[3]。微生物群可以通过提供营养、参与维生素的合成和血管的生成、抑制病原体生长、维持激素平衡和调节炎性反应来帮助维持体内平衡^[4]。在失衡的情况下，微生物群可以导致各种疾病甚至恶性肿瘤，还可以影响化疗、靶向免疫疗法的疗效以及术后并发症的发生，这些都与致癌信号通路的激活和细胞DNA的破坏有关^[5]。研究证实，微生物群与胰腺癌较高的肿瘤侵袭力、远处转移及对化疗药物不敏感等特征显著相关。最近，大多数基于临床样本或病例报告探讨了微生物群与胰腺癌免疫微环境之间的相关性，但其具体机制尚不清楚，特别是涉及的免疫途径和有益菌群的作用往往被忽视。进一步了解微生物群在胰腺癌免疫治疗中的作用，可以为胰腺癌提供更有效的治疗策略。

表1 微生物与胰腺癌的相关性研究

部位	微生物	患者例数		检测方法	作用	参考文献
部位	微生物	病例组	对照组	检测方法	作用	参考文献
口腔	长球奈瑟菌、轻型链球菌	10	10	qPCR	促癌	Farrell等^[21]
	牙龈卟啉单胞菌	405	416	血浆抗体检测	促癌	Michaud等^[22]
	放线杆菌	361	371	细菌16S测序	促癌	Fan等^[23]
	颗粒链菌	27	21	qPCR	促癌	Gaiser等^[6]
消化道	幽门螺杆菌	690	373	血浆抗体ELISA检测	促癌	Risch等^[24]
	念珠菌	34 829	34 829	Cox比例风险回归分析	促癌	Chung等^[19]
	拟杆菌门	85	57	Miseq测序	促癌	Ren等^[25]
肿瘤内	γ-变形菌纲	113	20	qPCR、细菌16S测序	耐药	Geller等^[26]
	假单胞菌、伊丽莎白金菌、变形杆菌、拟杆菌门、厚壁菌门	12	5	细菌16S测序	促癌	Pushalkar等^[27]

表1 微生物与胰腺癌的相关性研究

部位	微生物	患者例数		检测方法	作用	参考文献
部位	微生物	病例组	对照组	检测方法	作用	参考文献
口腔	长球奈瑟菌、轻型链球菌	10	10	qPCR	促癌	Farrell等^[21]
	牙龈卟啉单胞菌	405	416	血浆抗体检测	促癌	Michaud等^[22]
	放线杆菌	361	371	细菌16S测序	促癌	Fan等^[23]
	颗粒链菌	27	21	qPCR	促癌	Gaiser等^[6]
消化道	幽门螺杆菌	690	373	血浆抗体ELISA检测	促癌	Risch等^[24]
	念珠菌	34 829	34 829	Cox比例风险回归分析	促癌	Chung等^[19]
	拟杆菌门	85	57	Miseq测序	促癌	Ren等^[25]
肿瘤内	γ-变形菌纲	113	20	qPCR、细菌16S测序	耐药	Geller等^[26]
	假单胞菌、伊丽莎白金菌、变形杆菌、拟杆菌门、厚壁菌门	12	5	细菌16S测序	促癌	Pushalkar等^[27]

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