IMMU-50. IMPACT OF SARS-COV-2 MRNA VACCINES ON PD-L1 EXPRESSION IN INTRACRANIAL TUMORS

Abstract Although immune checkpoint inhibitor (ICI) effectiveness is correlated with intra-tumoral PD-L1 expression, there are no clinically available methods to improve sensitivity to ICIs by modulating PD-L1 expression. mRNA vaccines stimulate robust interferon-dependent innate immune activation leading to four-fold increases in PD-L1 expression on peripheral and intratumoral myeloid cells and enhanced sensitivity to immune checkpoint blockade in preclinical models (Sayour, Grippin, et al., NanoLetters, 2018; Mendez-Gomez, et al., Cell, 2024). We hypothesized that mRNA vaccines targeting SARS-COV-2 would similarly enhance PD-L1 expression in intracranial tumors. To test this hypothesis, we utilized institutional databases to identify 5,524 patients at our institution with pathology reports including the term “PD-L1” from August 2020 to November 2023. Pathological data and dates of SARS-COV-2 vaccination were compiled for each patient. Across the entire cohort (n=5,524), receipt of a SARS-COV-2 mRNA vaccine within 100 days of biopsy was associated with a 55% increase in mean tumor proportion score (TPS) (14% vs 8.9%, p=0.029). In the subset of patients with intracranial tumors (n=187), receipt of a SARS-COV-2 mRNA vaccine within 100 days of biopsy was associated with a massive increase in TPS (57% vs 7.2%, p<0.001). To evaluate the impact of this change on clinical outcomes with immunotherapy, we utilized a second institutional database to assemble a cohort of patients with Stage IV melanoma with intracranial metastasis treated with immune checkpoint blockade during the period August 2020 through November 2023. Patients who received a SARS-COV-2 vaccine within 100 days of initiation of ICI (n=10) exhibited numerically improved overall survival compared to those without SARS-COV-2 mRNA vaccine (n=38) (HR 0.50, 95% CI 0.22-1.2, p=0.06). Median overall survival was 545 days among patients without COVID mRNA vaccination and was not met among those with COVID mRNA vaccination. This data supports further investigation of the immune modulating effect of SARS-COV-2 mRNA vaccines in patients with intracranial tumors treated with immune checkpoint blockade.