Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Immunol. 2023 Sep 4;14:1238233. doi: 10.3389/fimmu.2023.1238233. eCollection 2023.
Despite tremendous efforts to exploit effective therapeutic strategies, most glioblastoma (GBM) inevitably relapse and become resistant to therapies, including radiotherapy and immunotherapy. The tumor microenvironment (TME) of recurrent GBM (rGBM) is highly immunosuppressive, dominated by tumor-associated macrophages (TAMs). TAMs consist of tissue-resident microglia and monocyte-derived macrophages (MDMs), which are essential for favoring tumor growth, invasion, angiogenesis, immune suppression, and therapeutic resistance; however, restricted by the absence of potent methods, the heterogeneity and plasticity of TAMs in rGBM remain incompletely investigated. Recent application of single-cell technologies, such as single-cell RNA-sequencing has enabled us to decipher the unforeseen diversity and dynamics of TAMs and to identify new subsets of TAMs which regulate anti-tumor immunity. Here, we first review hallmarks of the TME, progress and challenges of immunotherapy, and the biology of TAMs in the context of rGBM, including their origins, categories, and functions. Next, from a single-cell perspective, we highlight recent findings regarding the distinctions between tissue-resident microglia and MDMs, the identification and characterization of specific TAM subsets, and the dynamic alterations of TAMs during tumor progression and treatment. Last, we briefly discuss the potential of TAM-targeted strategies for combination immunotherapy in rGBM. We anticipate the comprehensive understanding of the diversity and dynamics of TAMs in rGBM will shed light on further improvement of immunotherapeutic efficacy in rGBM.
尽管人们付出了巨大的努力来开发有效的治疗策略，但大多数胶质母细胞瘤（GBM）不可避免地会复发，并对包括放疗和免疫疗法在内的治疗产生耐药性。复发性 GBM（rGBM）的肿瘤微环境（TME）高度免疫抑制，主要由肿瘤相关巨噬细胞（TAMs）组成。TAMs 由组织驻留的小胶质细胞和单核细胞衍生的巨噬细胞（MDMs）组成，它们对促进肿瘤生长、侵袭、血管生成、免疫抑制和治疗耐药性至关重要；然而，由于缺乏有效的方法，rGBM 中 TAMs 的异质性和可塑性仍未得到充分研究。单细胞技术的最近应用，如单细胞 RNA 测序，使我们能够破译 TAMs 的不可预见的多样性和动态，并确定调节抗肿瘤免疫的新 TAMs 亚群。在这里，我们首先回顾了 TME 的特征、免疫疗法的进展和挑战，以及 rGBM 中 TAMs 的生物学，包括它们的起源、分类和功能。接下来，从单细胞的角度，我们重点介绍了最近关于组织驻留小胶质细胞和 MDMs 之间区别的发现、特定 TAM 亚群的鉴定和特征描述，以及 TAMs 在肿瘤进展和治疗过程中的动态变化。最后，我们简要讨论了 TAM 靶向策略在 rGBM 联合免疫治疗中的潜力。我们预计，对 rGBM 中 TAMs 的多样性和动态的全面理解将为进一步提高 rGBM 中免疫治疗的疗效提供启示。
