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.