1050 Heat Shock Proteins Predict Clinical Response and Potentiate Local Immunogenicity After LITT for Glioblastoma

INTRODUCTION: Even given standard of care and the advent of new therapies, glioblastoma (GBM) is one of the deadliest forms of cancer. Laser interstitial thermal therapy(LITT) is a minimally invasive technique used to ablate intra-axial brain tumors. Non-ablative LITT-induced hyperthermia (33-43°C) increases intra-tumoral mutational burden and neoantigen production. Hyperthermia promotes neoantigen presentation via release of heat shock proteins(HSPs). HSPs are protein-folding chaperones that can present novel intracellular antigens for immune recognition. METHODS: We conducted immune deconvolution of bulk RNA-sequencing data obtained from The Cancer Genome Atlas, determining the correlation between 97 HSPs and tumor infiltration of CD8+,CD4+,B,Macrophage,Neutrophil,and Dendritic cells. We evaluated the association between expression of these HSPs and overall survival(OS). Additionally, we obtained pre-LITT biopsies for 9 patients consisting of responders and non-responders and conducted immunohistochemistry to identify spatial expression of HSPs. To validate our findings, we utilized next generation sequencing to determine genomic variations of identified HSPs, as well as identify other predictive biomarkers. RESULTS: We identified two HSPs for further investigation, SACS and HSPA5. SACS was associated improved survival based on TCGA data (14.9vs.11 months,HR:1.3,p<0.0001). HSPA5 was associated with worse outcomes (12.1vs.15.0 months,HR:0.73,p<0.0001). Based on immune deconvolution, HSPA5 was positively correlated with dendritic cell infiltration (r=0.50,p=6.1E-27). SACS was positively correlated with CD8+ infiltration(SACS:r=0.31,p=6.8E-11). IHC of 9 patients stratified based on OS demonstrated high SACS expression was associated with improved OS(p<0.05) after LITT. Immune cell infiltration was associated with therapeutic response after LITT using multiplex IHC. CONCLUSIONS: As we continue our immunohistochemical and genomic analysis, we hope to clarify the role HSPs play in potentiating immunogenicity in GBM. Further investigation into SACS and immune cell infiltration may inform how hyperthermia mediates improved response to LITT via neoantigen presentation.