Different T-cell subsets in glioblastoma multiforme and targeted immunotherapy

Wang, Hongsheng; Zhou, Huangao; Xu, Jianing; Lu, Yunpeng; Ji, Xiaoyun; Yao, Yizheng; Hou, Chao; Zhang, Jun; Zhang, Xiaochun; Yao, Shun; Wu, Yunqiu; Wan, Jie

doi:10.1016/j.canlet.2020.09.028

Cited by 52 publications

(39 citation statements)

References 87 publications

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“…The above fully immunocompetent model enables us to investigate the role of immune cells mediating an oncolytic virus expressing a full-length antibody with or without the Fcdependent effect. The immunosuppression TME of GBM, characterized by low activated T-cell infiltration and high ratio of TAMs, leads to tumor immune evasion 44 . TAMs have been found to be the major immune cells that promote tumor development in the GBM microenvironment 45,46 .…”

Section: Discussionmentioning

confidence: 99%

An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

Tian

Chen

et al. 2021

Nat Commun

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Oncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

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Section: Discussionmentioning

confidence: 99%

An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

Tian

Chen

et al. 2021

Nat Commun

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“…Additional blocking of CD40 further prolonged survival of tumor-bearing mice [171]. As described above, GBM is characterized by its immunosuppressive microenvironment [163,164]. Furthermore, Chongsathidkiet et al discovered a mechanism that hinders T cells from infiltrating GBM tumors [172].…”

Section: Immunotherapeutic Approaches Involving Chemokine Signalingmentioning

confidence: 96%

“…As chemokines are involved in the tracking and migration of immune cells [34,37,39,64], they contribute to the efficacy of these immunotherapeutic approaches. Nevertheless, GBM is characterized by its highly immunosuppressive nature which has been described in detail elsewhere [163,164]. In short, multiple factors contribute to the immune-privileged environment of GBM, namely, the blood-brain barrier, the absence of classical lymphatic vessels, immunosuppressive cells within the tumor microenvironment, e.g., regulatory T cells, protumoral TAMs and immunosuppressive factors released by glioma cells [164].…”

Section: Immunotherapeutic Approaches Involving Chemokine Signalingmentioning

confidence: 99%

Advances in Chemokine Signaling Pathways as Therapeutic Targets in Glioblastoma

Urbantat

Vajkoczy

Brandenburg

2021

Cancers

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With a median patient survival of 15 months, glioblastoma (GBM) is still one of the deadliest malign tumors. Despite immense efforts, therapeutic regimens fail to prolong GBM patient overall survival due to various resistance mechanisms. Chemokine signaling as part of the tumor microenvironment plays a key role in gliomagenesis, proliferation, neovascularization, metastasis and tumor progression. In this review, we aimed to investigate novel therapeutic approaches targeting various chemokine axes, including CXCR2/CXCL2/IL-8, CXCR3/CXCL4/CXCL9/CXCL10, CXCR4/CXCR7/CXCL12, CXCR6/CXCL16, CCR2/CCL2, CCR5/CCL5 and CX3CR1/CX3CL1 in preclinical and clinical studies of GBM. We reviewed targeted therapies as single therapies, in combination with the standard of care, with antiangiogenic treatment as well as immunotherapy. We found that there are many antagonist-, antibody-, cell- and vaccine-based therapeutic approaches in preclinical and clinical studies. Furthermore, targeted therapies exerted their highest efficacy in combination with other established therapeutic applications. The novel chemokine-targeting therapies have mainly been examined in preclinical models. However, clinical applications are auspicious. Thus, it is crucial to broadly investigate the recently developed preclinical approaches. Promising preclinical applications should then be investigated in clinical studies to create new therapeutic regimens and to overcome therapy resistance to GBM treatment.

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“…In order to carry out such an elegant task, glioma cells secrete a variety of cytokines, chemokines, and growth factors, which allows them to recruit and hijack cells both within the CNS and the periphery (Table 2). These non-neoplastic cells work in concert to create a unique immunosuppressive microenvironment that promotes tumor growth, survival, and invasion (Hattermann et al, 2014;Broekman et al, 2018;Brandao et al, 2019;DeCordova et al, 2020;Mohme and Neidert, 2020;Wang et al, 2021) (Figure 4; summarized in Table 3).…”

Section: Key Cellular Componentsmentioning

confidence: 99%

“…Furthermore, factors within the TME impair the cDC-mediated differentiation of T h 1 cells, recruitment of cytotoxic T-cells and promote activation of T regulatory cells through regulation of cDC production of IL-12, IL-10, and TGF-B (De Smedt et al, 1997;Hilkens et al, 1997;Kaliński et al, 1998;Platten et al, 2001;Zong et al, 2016;Flórez-Grau et al, 2018). Together these findings suggest that TA-cDCs likely contribute to both local and systemic immunosuppression Fallarino et al, 2006;Walker et al, 2006;Mahata et al, 2015 T cell suppression by cells of GME Increased infiltration of regulatory T cells TAM-mediated T cell suppression via iNOS, Arg1 and AHR activation GME-derived PGE2, IL6, IL10 and TGF-β, suppress T cell proliferation and effector function Hao et al, 2002;Kumar et al, 2016;Panek et al, 2019;Takenaka et al, 2019;Cao et al, 2020;Wang et al, 2021 Regulation of specific T cell molecular programs GBM-derived tenascin-C (TNC)-mediated inhibition of T cell proliferation and activation Increased T cell expression of PD-1, TIM-3, CTLA-4 and IDO-1 Imbalance of T H 1/T H 2 resulting in pro-tumor T H 2 bias IDO-mediated induction of regulatory T cells HIF-1a, ICOSLG, and IL2-mediated proliferation of regulatory T cells Kortylewski et al, 2005;Fallarino et al, 2006;Shimato et al, 2012;Mirzaei et al, 2017Mirzaei et al, , 2018Romani et al, 2018;Takashima et al, 2018;Woroniecka et al, 2018;Miska et al, 2019;Iwata et al, 2020 Ignorance Anatomical barriers promote antigen or T cell sequestration [e.g., BBB, bone marrow (BM)]…”

Section: Dendritic Cells (Dcs)mentioning

confidence: 99%

Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance

Mitchell

Shireman

Potchanant

et al. 2021

Front. Cell. Neurosci.

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According to classical dogma, the central nervous system (CNS) is defined as an immune privileged space. The basis of this theory was rooted in an incomplete understanding of the CNS microenvironment, however, recent advances such as the identification of resident dendritic cells (DC) in the brain and the presence of CNS lymphatics have deepened our understanding of the neuro-immune axis and revolutionized the field of neuroimmunology. It is now understood that many pathological conditions induce an immune response in the CNS, and that in many ways, the CNS is an immunologically distinct organ. Hyperactivity of neuro-immune axis can lead to primary neuroinflammatory diseases such as multiple sclerosis and antibody-mediated encephalitis, whereas immunosuppressive mechanisms promote the development and survival of primary brain tumors. On the therapeutic front, attempts are being made to target CNS pathologies using various forms of immunotherapy. One of the most actively investigated areas of CNS immunotherapy is for the treatment of glioblastoma (GBM), the most common primary brain tumor in adults. In this review, we provide an up to date overview of the neuro-immune axis in steady state and discuss the mechanisms underlying neuroinflammation in autoimmune neuroinflammatory disease as well as in the development and progression of brain tumors. In addition, we detail the current understanding of the interactions that characterize the primary brain tumor microenvironment and the implications of the neuro-immune axis on the development of successful therapeutic strategies for the treatment of CNS malignancies.

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Different T-cell subsets in glioblastoma multiforme and targeted immunotherapy

Cited by 52 publications

References 87 publications

An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

Advances in Chemokine Signaling Pathways as Therapeutic Targets in Glioblastoma

Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance

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