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

Abstract

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.

The Pathological Evaluation of Autophagy-Related Protein (LC3B) and Its Association with the Infiltration of Immune Cells in Glioma

“…In agreement with these researches, Kmiecik et al, (2013) wrote a similar conclusion and Cejalvo et al, (2020) reported that T lymphocytes were concentrated more in glioblastomas than grade II and grade III gliomas (P value: <0.001).…”

Tumor-Derived Pericytes Driven by EGFR Mutations Govern the Vascular and Immune Microenvironment of Gliomas

“…The analysis was conducted in a Macsquant10 flow Cytometry (Miltenyi). Lymphoid and myeloid subsets were defined as in [13].…”

Integrated analysis of the genomic and transcriptional profile of gliomas with isocitrate dehydrogenase-1 and tumor protein 53 mutations

“…In the LGG cohort, the patients with IDH1 and TP53 mutations seem to have many immunological changes than the patients with wild-type, for example, the anti-viral function (defense response to virus, negative regulation of viral process, and type I interferon signaling pathway), which might indicate that the immune status in the patients with IDH1 and TP53 mutations is different from the patients with wild-type. Previous studies have shown reduced infiltration of immune cells in IDH1 mutant gliomas and suppressed PD-L1 expression, 35,36 while TP53 GOF mutation had shown it promotes inflammation and has a profound effect on patient prognosis. 25 In KEGG pathway results, the patients with IDH1 and TP53 mutations suggest more correlation with the other viral infection, such as COVID-19, influenza A, measles, and Epstein-Barr virus, that might be the consequences of the suppression of immune function in these patients.…”