Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches.
Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches.
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DOI：
10.3390/cancers13246156
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发表时间：
2021-12-07
期刊：
影响因子：
5.2
通讯作者：
Pellegatta S
中科院分区：
文献类型：
--
作者：
Anghileri E;Patanè M;Di Ianni N;Sambruni I;Maffezzini M;Milani M;Maddaloni L;Pollo B;Eoli M;Pellegatta S
GBM细胞与肿瘤浸润性免疫成分之间的主动通信有助于建立一个免疫抑制环境，在这个环境中T细胞是稀缺和耗尽的。这种情况在复发时尤其加重，这对于GBM患者几乎是不可避免的。免疫治疗方法，包括检查点抑制剂，已经证明疗效有限，不能延长生存期或复发性GBM患者。然而，许多研究表明，T细胞启动在GBM微环境中是可能的，T细胞衰竭或功能障碍可以被重新编程。我们将回顾文献数据，并报道从树突状细胞治疗的复发性GBM患者中获得的原始结果，以证明微环境在预测免疫治疗反应和影响个性化治疗决策中的作用。关于胶质母细胞瘤（GBM）中免疫浸润的存在和功能的解释仍然存在争议。多年来，GBM一直被认为是一种冷肿瘤，效应细胞浸润较少，其特征是免疫抑制先天免疫细胞比例高，包括GBM相关的小胶质细胞/巨噬细胞（GAMs）。在这种情况下，检查点抑制剂的失败，特别是在复发性GBM （rGBM）中，使我们超越临床结果，考虑免疫细胞的观点。rGBM的肿瘤微环境可能特别恶劣，即使暴露于标准的免疫调节疗法，肿瘤浸润淋巴细胞（til）存在时，要么功能失调，要么最终耗尽。然而，在检查点阻断治疗后，有可能观察到适应性免疫细胞的特异性募集和有效的全身免疫反应。在这篇综述文章中，我们试图解决关于rGBM肿瘤和免疫微环境的现有知识。此外，重新研究了GAMs和TIL功能障碍诱导的免疫抑制，以解释遗传缺陷，这些遗传缺陷可以决定对治疗的耐药性，并在复发时操纵免疫微环境。因此，我们重新评估了一些接受树突状细胞免疫治疗的rGBM患者的微环境，目的是确定更好的治疗反应的预测性免疫指标。
Active communication between GBM cells and tumor-infiltrating immune components contributes to establishing an immunosuppressive environment where T cells are scarce and exhausted. This condition is particularly exacerbated upon recurrence, which is almost inevitable for GBM patients. Immunotherapeutic approaches, including checkpoint inhibitors, have demonstrated limited efficacy and failed to prolong survival or recurrent GBM patients. Nevertheless, many studies have shown that T cell priming is possible in the GBM microenvironment, and that T cell exhaustion or dysfunction can be reprogrammed. We will revisit data from the literature and report original results obtained from recurrent GBM patients treated with dendritic cells to demonstrate the role of the microenvironment in predicting immunotherapy response and influencing decisions for personalized therapies. The interpretation of the presence and function of immune infiltration in glioblastoma (GBM) is still debated. Over the years, GBM has been considered a cold tumor that is less infiltrated by effector cells and characterized by a high proportion of immunosuppressive innate immune cells, including GBM-associated microglia/macrophages (GAMs). In this context, the failure of checkpoint inhibitors, particularly in recurrent GBM (rGBM), caused us to look beyond the clinical results and consider the point of view of immune cells. The tumor microenvironment in rGBM can be particularly hostile, even when exposed to standard immunomodulatory therapies, and tumor-infiltrating lymphocytes (TILs), when present, are either dysfunctional or terminally exhausted. However, after checkpoint blockade therapy, it was possible to observe specific recruitment of adaptive immune cells and an efficient systemic immune response. In this review article, we attempt to address current knowledge regarding the tumor and immune microenvironment in rGBM. Furthermore, immunosuppression induced by GAMs and TIL dysfunction was revisited to account for genetic defects that can determine resistance to therapies and manipulate the immune microenvironment upon recurrence. Accordingly, we reevaluated the microenvironment of some of our rGBM patients treated with dendritic cell immunotherapy, with the goal of identifying predictive immune indicators of better treatment response.
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影响因子：
3.3
作者：
Carvalho da Fonseca, Anna Carolina;Wang, Huaqing;Fan, Haitao;Chen, Xuebo;Zhang, Ian;Zhang, Leying;Lima, Flavia Regina Souza;Badie, Behnam
通讯作者：
Badie, Behnam
影响因子：
7.2
作者：
Hung AL;Maxwell R;Theodros D;Belcaid Z;Mathios D;Luksik AS;Kim E;Wu A;Xia Y;Garzon-Muvdi T;Jackson C;Ye X;Tyler B;Selby M;Korman A;Barnhart B;Park SM;Youn JI;Chowdhury T;Park CK;Brem H;Pardoll DM;Lim M
通讯作者：
Lim M
影响因子：
50.3
作者：
Hara T;Chanoch-Myers R;Mathewson ND;Myskiw C;Atta L;Bussema L;Eichhorn SW;Greenwald AC;Kinker GS;Rodman C;Gonzalez Castro LN;Wakimoto H;Rozenblatt-Rosen O;Zhuang X;Fan J;Hunter T;Verma IM;Wucherpfennig KW;Regev A;Suvà ML;Tirosh I
通讯作者：
Tirosh I
影响因子：
7.3
作者：
Jan CI;Tsai WC;Harn HJ;Shyu WC;Liu MC;Lu HM;Chiu SC;Cho DY
通讯作者：
Cho DY
影响因子：
15.9
作者：
Antonios, Joseph P.;Soto, Horacio;Prins, Robert M.
通讯作者：
Prins, Robert M.