LGG-10. TUMOR-ASSOCIATED IMMUNE RESPONSE IN ANAPLASTIC PROGRESSION OF PXA

Pleomorphic xantoastrocytoma (PXA) is a typically well circumscribed astrocytic neoplasm that can progress to anaplastic PXA with an aggressive biologic behavior and worse prognosis. Histological features of anaplastic progression include increased proliferation, necrosis, microvascular proliferation, loss of pericellular reticulin, and increased infiltrative growth. Genetically anaplastic PXA is characterized by the combination of CDKN2A biallelic inactivation and oncogenic RAF kinase signaling, as observed in PXA, as well as a relatively small number of additional genetic alterations, with the most common being TERT amplification or promoter mutation (Phillips et al 2018). Common to both PXA and anaplastic PXA is the perivascular accumulation of lymphocytes. Given the potential importance of the immune response in brain tumors we asked whether the immune response in anaplastic PXA was different than that in PXA and in IDH-mutant diffuse glioma. To do this we used quantitative multiplex immunofluorescence of scanned slides and quantified the populations and phenotypes of T cells and microglia/macrophages in tumors identified from the UCSF Brain Tumor Center Biorepository and from the archives of the UCSF Neuropathology Division. All tumors were molecularly characterized by immunostaining and/or comprehensive genomic profiling. A total of 30 PXA, including 6 paired tumors before and after tumor progression, and 30 diffuse glioma were examined. Immunostaining for T cell subsets included CD3, CD8, and FOXP3 and for microglial/macrophages included Iba1, CD204, and CD163. Using quantitative multiplex immunostaining we assess immune cell subsets and their localization within the tissue highlighting the perivascular CD3+ lymphocytes. Our data suggest differences in the quantity and quality of immune cells in anaplastic PXA.