Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma

• DOI: 10.1136/jitc-2024-010173
• Publication Date: 2025-01-27T17:16:47Z
• Authors: Shin-Yi Chung; Yi-Chen Yeh; Chien-Jung Huang; Nai-Jung Chiang; Dennis Shin-Shian...; Ming-Hsien Chan; Meng-Lun Lu; Tzu-Sheng Hsu; Yi-Ping Hung; Chun-Nan Yeh; Michael Hsiao; Yu-Chan Chang; Yu-Chao Wang; Ming-Huang Chen
• Keywords: Tumor-infiltrating lymphocytes; Immune checkpoint; Gene signature

Background Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) have been implicated in response cancer. However, role difference TLSs TILs patients cholangiocarcinoma remains unclear. This study elucidates their contributions TME. Methods We examined 16 samples from single-arm, phase II trial nivolumab plus modified gemcitabine S-1 various datasets. Immunohistochemistry RNA sequencing were employed assess presence activity. Differential gene expression signature cell composition by GeoMx Digital Spatial Profiler Cancer Transcriptome Altas analysis. Results TLS-positive (N=7) demonstrated significantly better immunotherapy outcomes compared TLS-negative (N=9) patients, including higher objective rates (71% vs 0%) disease control (100% 67%). The correlated improved progression-free overall survival (p=0.03). associated “inflamed” tumors characterized substantial infiltration, involving T B cells. Gene analyses identified significant upregulation cell-related genes TLSs. Additionally, exhibited properties memory cells myeloid dendritic but lower levels innate TILs. within showed elevated precursor-exhausted-related cytotoxicity signature. Furthermore, had exhaustion signatures tumors. Clinical data corroborated these findings, PD-L1 LAG-3 Conclusion Our findings revealed that more exhausted PD-1 protein CCA which support our clinical finding. can predict favorable cholangiocarcinoma, highlighting potential as biomarker therapeutic target enhance treatment efficacy.