Abstract 744: Exploration of potential biomarkers associated with treatment outcomes in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant nivolumab plus paclitaxel and cisplatin chemoradiotherapy
Authors: Ta-Chen Huang, Jhe-Cyuan Guo, Chia-Chi Lin, Hung-Yang Kuo, Chien-Huai Chuang, Jason Chia-Hsien Cheng, Feng-Ming Hsu, Jang-Ming Lee, Pei-Ming Huang, Chih-Hung Hsu
Journal: Cancer Research (2025)

Abstract Background: In a phase II trial (neo-NTP-CRT, NCT05130684), the efficacy of adding nivolumab to paclitaxel and cisplatin-based neoadjuvant chemoradiotherapy (CRT) was tested in patients with locally advanced esophageal squamous cell carcinoma (ESCC) (n=17). The study reported a pathological complete response (pCR) rate of 24%, a median relapse-free survival and overall survival (OS) of 8 and 16 months, respectively. We conducted this exploratory analysis to investigate the potential immune-related biomarkers. Materials and Methods: Pretreatment endoscopy-biopsied tumor tissues were analyzed. Immunohistochemistry (IHC) was used to measure PD-L1 expression by clone SP142 (Ventana, Tucson, AZ, USA) on tumor cells (PD-L1-TC), immune cells (PD-L1-IC), and combined positive score (CPS), and to define mature tertiary lymphoid structure (mTLS) according to CD20 and CD23 expression (n=16). The expression of immune-related genes in ESCC tumor tissues was quantitated by PanCancer Immune Profiling and analyzed by nCounter® Analysis System (nanoString, Seattle, WA, USA) (n=12). 12-chemokine TLS signature was also analyzed. The association of PD-L1-TC, PD-L1-IC, CPS, mTLS, and TLS signature with pCR was examined by Chi-square test; the association with OS was examined by log rank test. The differences of various immune cells and immune-related functions between patients with and without pCR was investigated by t-test. Results: pCR rate was significantly higher in the patients with positive PD-L1 TC (100% vs 18%, p=0.019), high PD-L1 IC (100% vs 18%, p=0.019), and CPS≥5 (100% vs 10%, p=0.0006), and trended to be higher in patients with mTLS (50% vs 14%, p=0.19) and higher 12-chemokine TLS signature (75% vs 17%, p=0.077). OS trended to be longer in patients with positive PD-L1 TC (median: not reached vs 15 months; HR: 0.24, p=0.05) and CPS≥5 (median: 26 vs 15 months; HR: 0.19, p=0.069), and patients with high PD-L1 IC had numerically longer OS (median: 25 vs 16 months; HR: 0.42, p=0.38). mTLS was not associated with OS (median: 25 vs 25 months; HR: 0.91, p=0.88); however, patients with higher 12-chemokine TLS signature had better OS (median: 25 vs 14 months; HR: 0.23, p=0.042). The analysis of immune-related gene expression revealed patients with pCR had significantly higher abundance of TILs, lower amounts of Treg, exhausted CD8 T cells, and macrophages. Significantly higher B cell function, cytotoxicity function, and Toll-like receptor function was found in tumors of pCR patients. Conclusion: We found that PD-L1 expression and 12-chemokine TLS signature may be a potential predictor of the response to neoadjuvant nivolumab plus paclitaxel and cisplatin-based CRT. (grants: NCTRC200909, MOST 108-2314-B-002-076-MY3, MOHW 111-TDU-B-221-114006) Citation Format: Ta-Chen Huang, Jhe-Cyuan Guo, Chia-Chi Lin, Hung-Yang Kuo, Chien-Huai Chuang, Jason Chia-Hsien Cheng, Feng-Ming Hsu, Jang-Ming Lee, Pei-Ming Huang, Chih-Hung Hsu. Exploration of potential biomarkers associated with treatment outcomes in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant nivolumab plus paclitaxel and cisplatin chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 744.