Immunological Evasion in Glioblastoma

Magaña-Maldonado, Roxana; Chávez-Cortez, Elda Georgina; OlascoagaArellano, Nora Karen; Lopez-Mejia, Mariana; Maldonado-Leal, Fernando Manuel; Sotelo, Julio; Pineda, Benjamín

doi:10.1155/2016/7487313

Cited by 40 publications

(39 citation statements)

References 82 publications

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“…38 GBM tumor cells themselves possess a large arsenal of immunosuppressive mechanisms, spanning from programming tumorassociated macrophages into M2 macrophages and recruiting myeloid-derived suppressor cells (MDSC) to secretion of inhibitory molecules such as TGF-b, IL-10, prostaglandins, and many others. 39 Current efforts to increase the anti-tumor immune response in GBM patients include (but are not restricted to) tumor vaccination, 40 application of checkpoint inhibitors, 41 and the targeting of unconventional lymphocytes including gd T cells. 13,14,42 A precondition for any kind of immunotherapeutic strategy is a precise characterization of the immune system in GBM patients, and particularly the modulation by conventional (yet unsatisfactory) therapies.…”

Section: Discussionmentioning

confidence: 99%

In-depth immunophenotyping of patients with glioblastoma multiforme: Impact of steroid treatment

Chitadze

Flüh²,

Quabius

et al. 2017

OncoImmunology

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Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered. Here we performed an in-depth immunophenotyping of GBM patients and age-matched healthy controls and analyzed NKG2D ligand expression on primary GBM cells . We report that GBM patients have a compromised innate immune system irrespective of steroid (dexamethasone) medication. However, dexamethasone drastically reduced the number of immune cells in the blood of GBM patients. Moreover, higher counts of immune cells influenced by dexamethasone like CD45 lymphocytes and non-Vδ2 γδ T cells were associated with better overall survival. Higher levels of NKG2D ligands on primary GBM tumor cells were observed in patients who received radiochemotherapy, pointing towards increased immunogenic potential of GBM cells following standard radiochemotherapy. This study sheds light on how steroids and radiochemotherapy affect immune cell parameters of GBM patients, a pre-requisite for the development of new therapeutic strategies targeting the immune system in these patients.

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Section: Discussionmentioning

confidence: 99%

In-depth immunophenotyping of patients with glioblastoma multiforme: Impact of steroid treatment

Chitadze

Flüh²,

Quabius

et al. 2017

OncoImmunology

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show abstract

“…M2 macrophages not only inhibit tumor apoptosis and promote cell proliferation by activating NK-κB [ 26 ], but participated in tumor metastasis by releasing diverse pro-angiogenic factors such as VEGF, FGF2 and TNFα [ 27 ]. It is known that M2 macrophages can promote an immunosuppressive environment by secreting various immunomodulatory molecules such as IL-10, CCl2, CSF-1 and TGF-β [ 28 ]. Recently, high protein expression of CD163 is observed in oral squamous carcinoma [ 29 ], meningioma [ 30 ], bladder cancer [ 31 ], breast cancer [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer

et al. 2017

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CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibroblasts (Cafs). Besides, more CD163 positive macrophages and CD163 expressing gastric cancer cells are associated with tumor invasion and poor prognosis. Knocking-down CD163 in cancer cells could inhibit tumor growth in vivo. We also find various immune molecules which are correlated with CD163 in gastric cancer tissues and cell lines have positive staining in the cancer cells of clinical sample. Finally, we confirm CD163 is a novel target gene of STAT3 (signal transducer and activator of transcription 3) in gastric cancer. Our data indicate that CD163 may be a potential poor prognostic marker and therapeutic target for gastric cancer.

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“…The development of CAR-modified NK cells must overcome similar obstacles. Glioblastoma is one of the most lethal primary brain malignancies in adults and children, because of its highly invasive and metastatic characteristics (Magana-Maldonado et al, 2016 ). Neuroblastoma is a neuroendocrine tumor of early childhood and is the most common extracranial solid tumor that occurs in children (Matthay et al, 2016 ).…”

Section: Car-modified Nk Cell-based Immunotherapy To Treat Cancermentioning

confidence: 99%

Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV

et al. 2017

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Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body’s immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

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Immunological Evasion in Glioblastoma

Cited by 40 publications

References 82 publications

In-depth immunophenotyping of patients with glioblastoma multiforme: Impact of steroid treatment

In-depth immunophenotyping of patients with glioblastoma multiforme: Impact of steroid treatment

CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer

Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV

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