Glioblastoma‐activated pericytes support tumor growth via immunosuppression

Sena, Isadora F. G.; Paiva, Ana; Prazeres, Pedro H. D. M.; Azevedo, Patrick O.; Lousado, Luiza; Bhutia, Sujit K.; Салмина, А. Б.; Mintz, Akiva; Birbrair, Alexander

doi:10.1002/cam4.1375

Cited by 61 publications

(42 citation statements)

References 98 publications

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“…In relation with that, the main angiogenic factor, vascular endothelial growth factor (VEGF), can inhibit the function of T cells and increase the recruitment of regulatory T cells (Tregs) and MDSCs 30 . Moreover, it has been shown that pericytes can support tumor growth via immunsuppression 31 . However, once in the tumors, the immune cells can also induce changes in the vascular compartment, as they have a strong pro-angiogenic role 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature

Cejalvo

Gargini

Segura-Collar

et al. 2020

Preprint

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BackgroundGliomas remain refractory to all attempted treatments, including those using immune checkpoint inhibitors. The characterization of the tumor (immune) microenvironment has been recognized as an important challenge to get a mechanistic explanation for this lack of response and to improve the therapy of glial tumors.MethodsWe designed a prospective analysis of the hematopoietic cells of gliomas by flow cytometry. Tumors with or without isocytrate dehydrogenase 1/2 (IDH1/2) mutations were included in the study. The genetic profile and the presence of different molecular and cellular features of the gliomas were analyzed in parallel. The findings were validated in mouse glioma models.ResultsWe observed that few immune cells infiltrate mutant IDH1/2 gliomas and we distinguished two different profiles in their IDH1/2 wild-type counterparts. The first one has an important immune component, particularly enriched in myeloid cells with immunosuppressive features. The second group is more similar to mutant IDH1/2 gliomas, with few immune cells and a less immunosuppressive profile. Notably, we observed a direct correlation between the immune content and the presence of vascular alterations, which were associated with a reduced expression of Tau, a microtubule-binding-protein that controls the formation of tumor vessels in gliomas. Furthermore, overexpression of Tau was able to reduce the immune content in orthotopic mouse glioma models, delaying tumor growth.ConclusionsThere is a correlation between vascular alterations and the immune profile of gliomas, which could be exploited for the design of more successful clinical trials with immunomodulatory molecules.

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Section: Discussionmentioning

confidence: 99%

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature

Cejalvo

Gargini

Segura-Collar

et al. 2020

Preprint

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“…206,207 These active pericytes aid in immune suppression, remodeling of PVN, and protection of glioma stem cells (GSC) or glioma-initiating cells (GICs) from ischemic injuries. 208,209 Additionally, GSC recruits vascular pericytes via SDF1/CXCR4 signaling for angiogenesis. 210,211 GICs maintain self-renewal and differential properties by interacting with pericyte-derived endothelial cells via PDGF-NOS2-ID4 signaling.…”

Section: Role Of Neurovascular Unit In Ischemia and Glioma Astrocytesmentioning

confidence: 99%

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

Ghosh

Chakraborty

Sarkar

et al. 2019

Sig Transduct Target Ther

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Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences,~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.

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“…In relation with that, the main angiogenic factor, vascular endothelial growth factor (VEGF), can inhibit the function of T cells and increase the recruitment of regulatory Tregs and MDSCs [31]. Moreover, it has been shown that pericytes can support tumor growth via immunosuppression [32]. However, once in the tumors, the immune cells can also induce changes in the vascular compartment as they have a strong pro-angiogenic role [33,34].…”

Section: Discussionmentioning

confidence: 99%

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature.

Cejalvo

Gargini

Segura-Collar

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Gliomas remain refractory to all attempted treatments, including those using immune checkpoint inhibitors. The characterization of the tumor (immune) microenvironment has been recognized as an important challenge to get a mechanistic explanation for this lack of response and to improve the therapy of glial tumors. Methods: We designed a prospective analysis of the immune cells of gliomas by flow cytometry. Tumors with or without isocytrate dehydrogenase 1/2 (IDH1/2) mutations were included in the study. The genetic profile and the presence of different molecular and cellular features of the gliomas were analyzed in parallel. The findings were validated in mouse glioma models.Results: We observed that few immune cells infiltrate mutant IDH1/2 gliomas and we distinguished two different profiles in their IDH1/2 wild-type counterparts. The first one has an important immune component, particularly enriched in myeloid cells with immunosuppressive features. The second group is more similar to mutant IDH1/2 gliomas, with few immune cells and a less immunosuppressive profile. Notably, we observed a direct correlation between the immune content and the presence of vascular alterations, which were associated with a reduced expression of Tau, a microtubule-binding-protein that controls the formation of tumor vessels in gliomas. Furthermore, overexpression of Tau was able to reduce the immune content in orthotopic mouse glioma models, delaying tumor growth. Conclusions: Our results confirmed the reduced infiltration of immune cells in IDH1/2 mutant gliomas. Moreover, we have found that the immunological content distinguishes two groups of IDH1/2 wild-type gliomas, one highly enriched in immunosuppressive cells and one with few lymphocytes and myeloid cells. Our data indicated a direct correlation between the presence of vascular alterations and the entrance of leukocytes in gliomas. Interestingly, high levels of Tau inversely correlated with the vascular and the immune content of gliomas. Altogether, our results could be exploited for the design of more successful clinical trials with immunomodulatory molecules.

show abstract

Glioblastoma‐activated pericytes support tumor growth via immunosuppression

Cited by 61 publications

References 98 publications

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature.

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