2型神经纤维瘤病相关前庭神经鞘瘤肿瘤微环境研究进展

Research Progress on Tumor Microenvironment in Neurofibromatosis Type 2 Related Vestibular Schwannoma

2型神经纤维瘤病(neurofibromatosis type 2,NF2)是一种少见的常染色体显性遗传疾病。NF2基因定位于22q12.2染色体的抑癌基因,由于该基因发生突变引起的全身性多发肿瘤综合征。双侧前庭神经鞘瘤(bilateral vestibular schwannoma,BVS)是NF2的最显著特征。较散发性的前庭神经鞘瘤(vestibule schwannoma,VS)相比,术中观察NF2-BVS血供比较丰富,并且NF2肿瘤易复发,类似于低度恶性肿瘤。所以NF2-BVS与散发的VS是否是相同肿瘤有待进一步探索。NF2-BVS多以手术治疗为主,患者大多要面临多次手术的情况,并且术后多伴有听力减退等并发症,治疗效果及生存质量远不及散发性VS。随着对于肿瘤微环境(tumor microenvironment,TME)及肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)促进肿瘤生长方面研究的深入。基于TME的针对NF2-BVS的新型治疗方法探索十分有必要。文章概述NF2-BVS疾病的特点及目前治疗手段的不足,肿瘤相关巨噬细胞对于肿瘤生长的促进与抑制作用,细胞外基质(extracellular matrix,ECM)对于肿瘤生长的作用,VS细胞外基质的探索,基于ECN相关NF2-BVS治疗方法可行性的探索,结合对VS与BVS临床表现的差异,提出针对TME相关的VS创新疗法的展望。

Neurofibromatosis type 2(NF2)is a rare autosomal dominant disease.The NF2 gene is located in the tumor suppressor gene on chromosome 22q12.2.Systemic multiple tumor syndrome is caused by mutation of this gene.Bilateral vestibular schwannoma(BVS)is the most significant feature of NF2.Compared with sporadic vestibular schwannoma(VS),blood supply in NF2-BVS is relatively abundant and NF2 tumors are prone to recurrence,similar to low-grade malignant tumors.Therefore,similarities between NF2-BVS and sporadic VS need to be further studied.In addition,since NF2-BVS is mainly surgically treated and most patients require multiple operations,complications such as hearing loss are not uncommon with treatment outcomes and quality of life far less favorable than in sporadic VS.Advances in studies on tumor microenvironment(TME)and tumor associated macrophages(TAMs)that promote tumor growth prompt a need to explore new treatment methods for NF2-BVS based on TME.This review provides a summary of characteristics of NF2-BVS and the deficiencies in current treatment methods,promotion and inhibition of tumor growth by tumor associated macrophages,the role of extracellular matrix(ECM)on tumor growth,research on VS extracellular matrix,and studies on the feasibility of ECN related nf2-bvs treatment methods.Innovative therapies for VS in relation to TME that exploit the differences in clinical manifestations between VS and BVS are also discussed.