The current state of immunotherapy for gliomas: an eye toward the future

Fecci, Peter E.; Sampson, John H.

doi:10.3171/2019.5.jns181762

Cited by 79 publications

(69 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibitory immune checkpoints are responsible for the dampening of antitumor immune functions (37). The development of immune checkpoint blockade therapies, including anti-PD-1 and anti-CTLA4 therapies, has provided new avenues for cancer treatment (38).…”

Section: Discussionmentioning

confidence: 99%

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.

show abstract

Section: Discussionmentioning

confidence: 99%

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…More than four decades of efforts with variety of immunotherapeutic modalities yield limited successes in glioma. Glioma imbues numerous obstacles to successful immunotherapy, including tumor heterogeneity, low mutational burden, T-cell dysfunction, and poor immune access (Fecci and Sampson, 2019). Moreover, new finding reveals that tumor-directed sequestration of T cells in bone marrow severely restricts the access of T cells to tumors in the CNS (Chongsathidkiet et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Classification of diffuse lower‐grade glioma based on immunological profiling

Wang

et al. 2020

Molecular Oncology

View full text Add to dashboard Cite

Transcriptomic data derived from bulk sequencing have been applied to delineate the tumor microenvironment (TME) and define immune subtypes in various cancers, which may facilitate the design of immunotherapy treatment strategies. We herein gathered published gene expression data from diffuse lower‐grade glioma (LGG) patients to identify immune subtypes. Based on the immune gene profiles of 402 LGG patients from The Cancer Genome Atlas, we performed consensus clustering to determine robust clusters of patients, and evaluated their reproducibility in three Chinese Glioma Genome Atlas cohorts. We further integrated immunogenomics methods to characterize the immune environment of each subtype. Our analysis identified and validated three immune subtypes—Im1, Im2, and Im3—characterized by differences in lymphocyte signatures, somatic DNA alterations, and clinical outcomes. Im1 had a higher infiltration of CD8+ T cells, Th17, and mast cells. Im2 was defined by elevated cytolytic activity, exhausted CD8+ T cells, macrophages, higher levels of aneuploidy, and tumor mutation burden, and these patients had worst outcome. Im3 displayed more prominent T helper cell and APC coinhibition signatures, with elevated pDCs and macrophages. Each subtype was associated with distinct somatic alterations. Moreover, we applied graph structure learning‐based dimensionality reduction to the immune landscape and revealed significant intracluster heterogeneity with Im2 subtype. Finally, we developed and validated an immune signature with better performance of prognosis prediction. Our results demonstrated the immunological heterogeneity within diffuse LGG and provided valuable stratification for the design of future immunotherapy.

show abstract

“…Immunotherapy options remain limited for GBM, despite the success of these treatment modalities in pre-clinical models and other solid tumors [31][32][33][34] . The immunosuppressive tumor microenvironment mainly consisting of myeloid cells is one of the major factors limiting the efficacy of existing treatment options 9 .…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cell subsets drive glioblastoma growth in a sex-specific manner

Bayik

Zhou

Park

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractMyeloid-derived suppressor cells (MDSCs) that block anti-tumor immunity are elevated in glioblastoma (GBM) patients. However, the distinct contribution of monocytic (mMDSC) versus granulocytic (gMDSC) subsets has yet to be determined. We observed that mMDSCs were enriched in the male tumor microenvironment, while gMDSCs were elevated in the circulation of female GBM models. Depletion of peripheral gMDSCs extended the survival only in female mice. Using gene expression signatures coupled with network medicine analysis, we demonstrated in pre-clinical models that mMDSCs could be targeted with anti-proliferative agents in males, whereas gMDSC function in females could be inhibited by IL-1β blockade. Analysis of patient data confirmed that proliferating mMDSCs were the predominant population in male tumors, and that a high gMDSC/IL-1β gene signature correlated with poor prognosis of female patients. These findings demonstrate that MDSC subsets differentially drive immune suppression in a sex-specific manner and can be leveraged for therapeutic intervention in GBM.Statement of SignificanceSexual dimorphism at the level of MDSC subset prevalence, localization and gene expression profile comprises a therapeutic opportunity. Our results indicate that chemotherapy can be used to target mMDSC in males, while IL-1 pathway inhibitors can provide benefit to females through blockade of gMDSC function.

show abstract

The current state of immunotherapy for gliomas: an eye toward the future

Cited by 79 publications

References 71 publications

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

Classification of diffuse lower‐grade glioma based on immunological profiling

Myeloid-derived suppressor cell subsets drive glioblastoma growth in a sex-specific manner

Contact Info

Product

Resources

About