The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. Materials and Methods A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. Results The density of CD8 + T cells, FoxP3-CD4 + helper T cells, and FoxP3 + CD4 + regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3-or TIM3-expressing CD8 + T cell and FoxP3-CD4 + helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3-CD4 + helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p = 0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3-CD4 + helper T cells in the tumor margin was independently associated with favorable PFS and OS. Conclusion The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3-CD4 + helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Background: Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. Methods: We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. Results: A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9 ± 5.0 mm; short axis, 4.3 ± 3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0 ± 4.0 mm; short axis, 3.0 ± 2.0 mm; all p < .001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively. Conclusions: The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.