Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of theNF1tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss ofNF1heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)—benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role ofNF1(Nf1)haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role ofNf1+/-immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care.
1型神经纤维瘤病（NF1）是一种常见的遗传性疾病，可导致外周神经系统良性和恶性肿瘤的发生。该病由NF1肿瘤抑制基因的种系致病性变异或缺失引起，该基因编码的神经纤维瘤蛋白是p21 RAS的负调控因子。在神经鞘源性肿瘤的起源细胞——施万细胞（SCs）中，NF1杂合性缺失会导致丛状神经纤维瘤（PNF）的形成。PNF是一种良性但结构复杂的肿瘤，累及多个神经束，并由大量浸润性基质细胞和免疫细胞构成。PNF的发生和发展受施万细胞与免疫细胞（包括肥大细胞、巨噬细胞和T细胞）之间动态相互作用的调控。本文综述了该领域的研究现状及关键知识空白，重点探讨NF1单倍体不足对免疫细胞功能的影响，以及施万细胞谱系状态对肿瘤微环境中免疫细胞募集和功能的潜在作用。此外，我们回顾了新兴证据，这些证据表明Nf1+/-免疫细胞在神经纤维瘤向恶性外周神经鞘瘤（MPNST）的进展过程中具有双重作用：一方面促进PNF的发生，另一方面可能抑制丛状和非典型神经纤维瘤前体病变的恶性转化。最后，我们强调这些发现的潜在意义，并呼吁进一步研究不同免疫细胞亚群在肿瘤发生、进展和恶性转化各阶段的具体作用，以推动创新诊疗方法的发现与转化，最终实现基于风险分层的精准医疗。
肿瘤(癌症)患者之家