Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer
Authors: Hatta Kousuke , Tanaka Ryota , Kimura Kenjiro , Eguchi Shinpei , Ohira Go , Shinkawa Hiroji , Nishio Kohei , Kinoshita Masahiko , Kurihara Shigeaki , Kushiyama Shuhei , Kawaguchi Takahito , Tani Naoki , Nakanishi Koichi , Yoshida Mizuki , Ishizawa Takeaki 
Published: March 2024

Abstract
Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs).
Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples.
Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p &lt; 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME.
Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells.
Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6884.