Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of rare tumors that are increasing in prevalence. The complex tumor immune microenvironment (TIME) plays an important role in tumor development and the response to immunotherapy but is poorly understood. In this review, the components of the TIME are described in detail, including discussion about infiltrating immune cells, the immune checkpoint system, the cytokine and chemokine milieu, and immunomodulatory factors. Moreover, a comparison between TIMEs among different types of GEP-NENs and the interplay among the TIME, tumor cells, and the stromal microenvironment is described. Novel treatment options for GEP-NENs and potential biomarkers for the immune response are also characterized. We provide a comprehensive generalized review of the TIME that can inform GEP-NEN treatment strategies.

胃肠道胰腺神经内分泌肿瘤（GEP-NENs）是一组罕见肿瘤，其患病率呈上升趋势。复杂的肿瘤免疫微环境（TIME）在肿瘤发展和对免疫疗法的反应中起着重要作用，但了解甚少。在本综述中，将详细描述TIME的组成部分，包括有关浸润免疫细胞，免疫检查点系统，细胞因子和趋化因子环境以及免疫调节因子的讨论。此外，描述了不同类型的GEP-NEN之间的TIME之间的比较以及TIME，肿瘤细胞和基质微环境之间的相互作用。还表征了GEP-NENs的新治疗选择和免疫应答的潜在生物标志物。