ATIM-25. NEOADJUVANT PD-1 ANTIBODY BLOCKADE IS ASSOCIATED WITH FOCAL UPREGULATION OF PD-L1 AND CD8 T CELL INFILTRATE IN RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: The use of anti-PD-1 therapy, pembrolizumab, has shown minimal therapeutic effect as an adjuvant treatment in glioblastoma, but its efficacy as a neoadjuvant in recurrent glioblastoma setting has yet to be established. METHODS: The Ivy Foundation Early Phase Clinical Trials' Consortium conducted a randomized, multi-institution Phase I clinical trial to evaluate the immune response and survival following neoadjuvant and adjuvant therapy with pembrolizumab in thirty patients with recurrent, surgically resectable glioblastoma. Formalin-fixed paraffin embedded tissue was stained using multiplex immunohistochemistry to spatially visualize and quantify the following markers: CD8, PD-1, CD45, GFAP, and PD-L1. RESULTS: The density of tumor infiltrating CD8 T-cells was not statistically different between groups, but distinctly variable in the neoadjuvant treatment group. PD-1 expression across both treatment groups co-localized with CD8 T-cells, though 9 neoadjuvant and only 3 adjuvant samples had appreciable PD-1 detected. Samples with the highest percentage of PD-L1 expression and double positive CD8/PD-1 cell population were present in both groups. Notable CD45/PD-L1 populations were found in 3 neoadjuvant treated samples, with only 1 in the adjuvant group. Samples were classified as having either constitutive, focal, or negative PD-L1 expression pattern with varying degrees of CD8 infiltrate. 7 neoadjuvant patients and 3 adjuvant patients exhibited a focal phenotype with a high CD8 infiltrate. Neoadjuvant samples exhibiting focal PD-L1 expression also had a higher median survival compared to the corresponding adjuvant group (p=0.035, Mantel-Cox log rank). CONCLUSION: Classification of tumors based on PD-L1, CD8, and PD-1 IHC may be predictive of outcome and therapeutic effect. We identified a subset of patients with focal expression of PD-L1 with increased survival. This suggests that focally expressed PD-L1, perhaps induced on tumor and immune infiltrate by the presence of an antitumor CD8 response, is a biomarker that is predictive of a positive response to anti-PD-1 checkpoint blockade.