Difference in Immunosuppressive Cells Between Peritumoral Area and Tumor Core in Glioblastoma

Tamura, Ryota; Ohara, Kentaro; Sasaki, Hidenao; Morimoto, Yukina; Kosugi, Kenzo; Yoshida, Kazunari; Toda, Masahiro

doi:10.1016/j.wneu.2018.08.133

Cited by 31 publications

(32 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could suggest a stronger recruitment of immune cells by the tumor preventing their accumulation in the periphery. Notably, previous papers reported that vascular features differed between the PTA and TC, probably leading to the prevalent localization of immune cells in this area [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…IDO was present in almost all of the TC samples tested and none of the PTA samples. It is interesting to note that VEGF, besides its angiogenic role, stimulates pro-tumoral immunity, triggering distinct immunosuppressive mechanisms [ 33 , 44 ]. We and others have already shown that VEGF expression is lower in the PTA compared to that in the TC.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma

Rahimi

Minasi

Ugolini

et al. 2020

JPM

View full text Add to dashboard Cite

Background: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. Methods: The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. Results: CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. Conclusion: Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma

Rahimi

Minasi

Ugolini

et al. 2020

JPM

View full text Add to dashboard Cite

show abstract

“…This critical concept has since been replicated in other tumor models, including pancreatic and lung adenocarcinoma [ 84 , 85 ]. Moreover, recent studies have shown a select spatial distribution of the resident and blood-derived macrophages within tumor lesions, which has been observed in both human and mouse GBM [ 86 , 87 , 88 ]. Specifically, these studies show that resident microglia tend to be located in the tumor periphery, while monocytes and monoMacs are more likely to reside within the tumor core.…”

Section: Immune and Stromal Landscape In Gbmmentioning

confidence: 99%

The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

Desland

Hormigo

2020

IJMS

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.

show abstract

“…HIF-1 would repress core-derived glioma cell differentiation through the suppression of Smad activation (Pistollato et al, 2009a , b ), maintaining a higher number of stem cells that express greater levels of the DNA repair protein MGMT (O 6 -methylguanine-DNA-methyltransferase) and consequently turn to be more radioresistant (Pistollato et al, 2009a , 2010 ). Also, low oxygen tension leads vascular ECs within the hypoxic niche to produce several factors, such as VEGF-A, which confer a more aggressive behavior to glioma CSCs and polarize immune cells into an immunosuppressive phenotype, as it is demonstrated by tumor-associated macrophage (TAM) M2 polarization, increased regulatory T cells, and higher rates of PD-1 + CD8 + T cells, leading to treatment resistance to traditional and modern approaches such as immunotherapy (Escribese et al, 2012 ; Tamura et al, 2018 , 2019a , b ) ( Figure 2 ).…”

Section: Role Of Tumor Microenvironment In Glioma Biologymentioning

confidence: 99%

Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment

Ruiz‐Garcia

Alvarado-Estrada

Schiapparelli

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and devastating primary brain tumor, leading to a uniform fatality after diagnosis. A major difficulty in eradicating GBM is the presence of microscopic residual infiltrating disease remaining after multimodality treatment. Glioma cancer stem cells (CSCs) have been pinpointed as the treatment-resistant tumor component that seeds ultimate tumor progression. Despite the key role of CSCs, the ideal preclinical model to study the genetic and epigenetic landmarks driving their malignant behavior while simulating an accurate interaction with the tumor microenvironment (TME) is still missing. The introduction of three-dimensional (3D) tumor platforms, such as organoids and 3D bioprinting, has allowed for a better representation of the pathophysiologic interactions between glioma CSCs and the TME. Thus, these technologies have enabled a more detailed study of glioma biology, tumor angiogenesis, treatment resistance, and even performing high-throughput screening assays of drug susceptibility. First, we will review the foundation of glioma biology and biomechanics of the TME, and then the most up-to-date insights about the applicability of these new tools in malignant glioma research.

show abstract

Difference in Immunosuppressive Cells Between Peritumoral Area and Tumor Core in Glioblastoma

Cited by 31 publications

References 29 publications

Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma

Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma

The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment

Contact Info

Product

Resources

About