Abstract 525: Immune-oncologic shift in programmed death-ligand 1 expression and microsatellite instability after neoadjuvant chemoradiation therapy in locally advanced rectal cancer

Abstract

Abstract Purpose: We designed this study to evaluate relations between microsatellite instability (MSI) status and programmed death-ligand 1 (PD-L1) and tumor response following neoadjuvant concurrent chemoradiation therapy (CCRT) in locally advanced rectal cancer. Materials and methods: In the prospective study, we collected 54 rectal adenocarcinoma patients who underwent neoadjuvant concurrent chemoradiation therapy between August 2016 and December 2017. With exclusion criteria, we finally included 24 patients and evaluated the PD-L1 expression using immunohistochemistry (IHC) and tested the MSI status with pre- and post- CCRT samples. Human colorectal cell lines DLD 1, HT-29 and HCT116 were obtained and cell morphology, cell viability, and PD-L1 expressions were evaluated using flow cytometry 24, 48 and 72 hours after irradiation. Using 4-fields box technique, 50.4 to 54 Gy in daily 1.8Gy fractions of radiation was delivered to pelvis including rectal mass and surgery was performed 6 to 8 weeks after completion of neoadjuvant CCRT. Tumor response was estimated by using Mandard grading system. Results: According to the tumor regression grade, patients were classified into two groups; responder (grade 0, 1 or 2; 9 patients, 37.5%) and non-responder (grade 3 or 4; 15 patients, 62.5%). Between the two groups, there was no statistically significant differences in several tumor characteristics including histologic type, lymphocytic response, tumor budding, BRAF or K-ras mutations except tumor stage; more patients with advanced T stage in non-responder (p = 0.019). MSI-high status was reported in two responders (25%), but no one with pre-CCRT MSI-high status in non-responder group (relative risk = 3.143, 95% CI = 1.705 - 5.794). High PD-L1 expression on tumor marginally significantly increased from 16.7% before CCRT to 45.0% after CCRT by IHC (P = 0.053), especially in non-responder group. PD-L1 gene expression by irradiation in three human cell lines using flow cytometry analysis was increased, mostly in radio-resistant cell line, DLD 1. Conclusion: This prospective study verified the chemoradiation-induced immune-oncologic shift toward increases in PD-L1 expression that may be associated with radio-resistance. MSI status was associated with tumor response after chemoradiotherapy for locally advanced rectal cancer. Key words: Locally advanced rectal cancer, neoadjuvant concurrent chemoradiation therapy, tumor regression, microsatellite instability, programmed death-ligand Note: This abstract was not presented at the meeting. Citation Format: SungUk Bae, Hye Won Lee, Sang Jun Byun, Woon Kyung Jeong, Seong Kyu Baek. Immune-oncologic shift in programmed death-ligand 1 expression and microsatellite instability after neoadjuvant chemoradiation therapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 525.