Checkpoint expression pre and post chemoradiation in operable esophageal cancer.
139 Background: PD-L1 expression has been reported in 40% of gastroesophageal cancers, but little data exists with regards to expression of other immune checkpoints. Here, we examined baseline expression levels for multiple immune modulators in 31 resected esophageal adenocarcinomas (EAC) and investigated the change in expression levels post-chemoradiation. Methods: Slides were stained on a Ventana BenchMark ULTRA automated stainer for CTLA-4 (Santa Cruz Clone F-8, dilutions 1:100) and PD-L1 (Dako clone 22C3 prediluted). Tonsil tissue was used as a control for lymphocytes, and a provided tumor control was used for PD-L1. Positivity was classified as > 1%, and the stained cell type was recorded (lymphocytes or tumor). Additionally, laser capture microdissection was performed, and RNA was isolated and pre-amplified to determine expression levels of TIM-3, GITR, IDO-1, LAG-3, CD-137, OX-40, and KIR-3 using RT-PCR. Gene expression was calculated using the ΔΔ -Ct method, and intergroup comparisons were performed and normalized against a cohort of 15 pathologically confirmed normal esophageal epithelium cases. Results: Post-chemoradiation cases demonstrated increased expression for PD-L1, when compared to matched pre-chemoradiation controls [p-value = 0.0098]. Similarly, all immune modulators profiled by gene expression were significantly upregulated in matched post vs. pre samples, except for CD-137. There was no significant difference in percentage of 4-fold or more upregulation based on PD-L1 status for IDO-1, OX-40, CD-137 and KIR-1, indicating that these markers may function independently of PD-L1 positivity. Conclusions: PD-1 inhibiton in both the neoadjuvant and adjuvant setting is currently being investigated in EAC, but future studies may look to select patients according to personalized checkpoint expression patterns. [Table: see text]
Kelly, RJ; Zaidi, AH; Smith, M; Omstead, AN; Kosovec, JE; Matsui, D; Martin, SA; Finley, GG; Silverman, JF; Werts, ED; Jobe, BA
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