New Study Identifies Immune Cell Target for Blocking Tumor Growth

Previous studies from the laboratory of NF Center director, David H. Gutmann, MD, PhD, have shown that immune system-like cells, called microglia, are important non-cancerous regulators of NF1 optic glioma formation and growth. Using a combination of RNA sequencing, genetically engineered mouse strains, and human tumor specimens, Amanda de Andrade Costa and colleagues discovered that brain tumor-associated microglia express a protein called CD11A.
In this study, recently published in the journal Neuro-Oncology, Dr. Costa found that CD11A was not only expressed on microglia in numerous strains of Nf1-mutant mice that develop optic gliomas, but also on human brain tumor-associated microglia. To determine whether CD11A was also important for microglia function, Dr. Jit Chatterjee, another postdoctoral fellow in the Gutmann laboratory, used microglia from mice lacking CD11a, and showed that these CD11a-deficient microglia had reduced migration and expression of a key growth factor needed for Nf1 mouse optic glioma growth. Consistent with an essential role for CD11a-expressing microglia in controlling Nf1 optic glioma growth, Dr. Costa used antibodies to block CD11a, resulting in reduced tumor growth in vivo.
Taken together, these findings establish CD11A as a critical microglia regulator of NF1 optic glioma growth, suggesting alternative treatment strategies for pediatric brain tumors.

De Andrade Costa A, Chatterjee J, Cobb O, Sanapala S, Guo X, Dahiya S, Gutmann DH. RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth. Neuro Oncol. 2021 May 27:noab130. doi: 10.1093/neuonc/noab130. Online ahead of print. PMID: 34043012