IMMU-25. PROGRAMMED CELL DEATH-LIGAND 1 (PD-L1) IS NOT EXPRESSED IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TUMOR CELLS

Abstract

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a pediatric high grade, infiltrative tumor that arises in the pons. It is the leading cause of brain tumor related death in children. Despite increased understanding of the genetics and epigenetics of DIPG, development of in vivo research models, and several clinical trials, standard of care and survival has not improved. One avenue that has yet to be explored in DIPG is the use of immune checkpoint inhibitors such as the anti-PD-1 and PD-L1 monoclonal antibodies, Nivolumab and Pembrolizumab, respectively. PD-1/PD-L1 checkpoint inhibition is currently being used to treat certain solid tumors, including melanoma and non-small cell lung cancer. In addition, two pediatric glioblastoma multiforme cases secondary to bi-allelic mismatch repair deficiency responded to treatment with Nivolumab. Evidence of immune infiltration and PD-1/PD-L1 expression was seen in these two tumors. Similarly, there may be a subset of DIPG that may respond to inhibiting the PD-1/PD-L1 axis. METHODS: To test this hypothesis, immunohistochemistry was performed for PD-L1 (SP142 clone), CD4 and CD8 in DIPG tumor samples using formalin-fixed paraffin-embedded tissues from autopsy, and appropriate positive and negative controls. PD-L1 (n=31) was evaluated as percentage of positive tumor cells. CD4 and CD8 (n=20) expression was assessed from 0 to 3+ based on average number of positive lymphocytes in four high power fields. RESULTS: Membranous PD-L1 expression was negative in each of the 31 cases characterized. There was low expression of CD4 (1+) in 11 out of 20 cases and CD8 was moderately expressed in 19 cases (1-2+). CONCLUSIONS: Targeting the PD-1/PD-L1 axis may have limited efficacy against DIPG. However, since tumor infiltrating lymphocytes are present, alternate immune evasion mechanisms, such as IDO and CTLA-4, should be evaluated in order to further characterize the immune microenvironment and assess the potential of immunotherapy against DIPG.