Menna Grazia, Mattogno Pier Paolo, Donzelli Carlo Maria, Lisi Lucia, Olivi Alessandro, Della Pepa Giuseppe Maria
Institute of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Institute of Pharmacology, Catholic University of Rome, 00168 Rome, Italy.
Brain Sci. 2022 May 31;12(6):718. doi: 10.3390/brainsci12060718.
: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.
自从发现肿瘤相关免疫细胞以来，人们对理解这些细胞与肿瘤细胞之间相互作用的潜在机制的兴趣与日俱增。最近引入了一种“种子与土壤”的方法来描述胶质母细胞瘤（GBM）的情况：肿瘤微环境充当肥沃的“土壤”，并与“种子”（神经胶质和干细胞部分）相互作用。在接下来的文章中，我们对当前有关胶质瘤相关巨噬细胞和小胶质细胞（GAMs）以及胶质瘤肿瘤微环境（TME）中的小胶质细胞和巨噬细胞特征的证据进行了系统综述。使用以下搜索词在PubMed Medline和Scopus上进行了在线文献搜索：“((胶质瘤相关巨噬细胞或GAM或小胶质细胞) AND (胶质母细胞瘤肿瘤微环境或TME))”。最近一次对与该主题相关文章的搜索是在2022年2月进行的。文献搜索共产生349条结果。共发现235项研究与我们的研究问题相关，并对其进行了资格评估。经过全文审查，58篇文章被纳入综述。根据重点，综述的论文进一步分为三类：（1）小胶质细胞维持免疫稳态和预防自身免疫；（2）小胶质细胞与去分化和干细胞样胶质母细胞瘤细胞的相互作用；（3）小胶质细胞的迁移行为及其激活模式。侵袭性生长、不可避免的复发以及对免疫疗法的反应不佳，促使人们有必要从不同角度关注GBM TME，以可能厘清其作为肿瘤进展的肥沃“土壤”的作用，并在其中确定可行的治疗靶点。在此背景下，我们的系统综述证实小胶质细胞在促进GBM进展和治疗后复发中起至关重要的作用。对小胶质细胞 - 胶质瘤相互作用的正确而广泛的理解有助于理解这种复杂疾病的生理病理学，可能为改善治疗开辟新途径。
