Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: implications for development of immunotherapy.

Abstract

Background:

Diffuse intrinsic pontine glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically; however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG.

Methods:

Tumor microarrays were stained for infiltrating immune cells. RNA was isolated from snap-frozen tumor tissue and Nanostring analysis performed. DIPG and glioblastoma cells were co-cultured with healthy donor macrophages, T cells, or natural killer (NK) cells, and flow cytometry and cytotoxicity assays performed to characterize the phenotype and function, respectively, of the immune cells.

Results:

DIPG tumors do not have increased macrophage or T-cell infiltration relative to nontumor control, nor do they overexpress immunosuppressive factors such as programmed death ligand 1 and/or transforming growth factor β1. H3.3-K27M DIPG cells do not repolarize macrophages, but are not effectively targeted by activated allogeneic T cells. NK cells lysed all DIPG cultures.

Conclusions:

DIPG tumors have neither a highly immunosuppressive nor inflammatory microenvironment. Therefore, major considerations for the development of immunotherapy will be the recruitment, activation, and retention of tumor-specific effector immune cells.

• Authors: Nicole A P Lieberman, Kole DeGolier, Heather M Kovar, Amira Davis, Virginia Hoglund, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Scott N Furlan, Nicholas A Vitanza, Sarah E S Leary, Courtney A Crane
• Journal: Neuro-oncology (Neuro Oncol) Vol. 21 Issue 1 Pg. 83-94 (01 01 2019) ISSN: 1523-5866 [Electronic] England
• PMID: 30169876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Adolescent
• Adult
• Biomarkers, Tumor (genetics)
• Brain Stem Neoplasms (genetics, immunology, pathology, therapy)
• Case-Control Studies
• Child
• Child, Preschool
• Diffuse Intrinsic Pontine Glioma (genetics, immunology, pathology, therapy)
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Humans
• Immunity, Cellular (immunology)
• Immunotherapy
• Infant
• Infant, Newborn
• Male
• Mutation
• Prognosis
• Survival Rate
• Tumor Microenvironment (immunology)
• Young Adult