Xiuxing Chen1,2,3, Ziming Du1,4,5, Mayan Huang1,6, Deshen Wang1,2, William Pat Fong1,2, Jieying Liang1,2, Lei Fan7, Yun Wang1,8, Hui Yang1,2, Zhigang Chen1,2, Mingtao Hu1,2, Ruihua Xu9,10, Yuhong Li11,12. 1. State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, 510060, People's Republic of China. 2. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. 3. Department of Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China. 4. Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of China. 5. Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. 6. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. 7. School of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, People's Republic of China. 8. Department of Hematologic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. 9. State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, 510060, People's Republic of China. xurh@sysucc.org.cn. 10. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. xurh@sysucc.org.cn. 11. State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, 510060, People's Republic of China. liyh@sysucc.org.cn. 12. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. liyh@sysucc.org.cn.
Abstract
BACKGROUND: Exosomal PD-L1 (exoPD-L1) could induce immunosuppression functionally, thus impairing patients' survival in melanoma, NSCLC, and gastric cancer. However, no evidence demonstrates the feasibility of circulating exoPD-L1 and soluble PD-L1 (sPD-L1) as biomarkers for prognosis and early recurrence in colorectal liver metastasis (CRLM) patients following hepatectomy or their association with T cell infiltration at liver metastases. METHODS: In cohort 1, exoPD-L1 and sPD-L1 were preoperatively tested using ELISA. CD3, CD8, granzyme B (GB) and PD1 expressed at liver metastases were evaluated using immunohistochemistry. In cohort 2, exoPD-L1 and sPD-L1 were detected at baseline, before hepatectomy, after hepatectomy, and after disease progression. RESULTS: In cohort 1, higher preoperative exoPD-L1 or sPD-L1 significantly impaired RFS (exoPD-L1, P = 0.0043; sPD-L1, P = 0.0041) and OS (exoPD-L1, P = 0.0034; sPD-L1, P = 0.0061). Furthermore, preoperative exoPD-L1 was negatively correlated with CD3 + T-lymphocytes infiltrated at tumor center (CT), and GB and PD1 were expressed at tumor invasive margin (IM). Preoperative sPD-L1 was negatively correlated with CD3 + and CD8 + T-lymphocytes' infiltration at IM and CT, GB and PD1 expression at IM. In cohort 2, exoPD-L1 and sPD-L1 levels decreased following hepatectomy but increased when tumor progressed. Moreover, higher postoperative exoPD-L1 and sPD-L1 or a small reduction in exoPD-L1 and sPD-L1 levels after hepatectomy suggested higher early recurrence rate. CONCLUSIONS: Both preoperative exoPD-L1 and sPD-L1 had promising prognostic values and were associated with T cell infiltration at liver metastases in CRLM patients following hepatectomy. Dynamically tracking exoPD-L1 and sPD-L1 levels could monitor disease status and detect early recurrence.
BACKGROUND: Exosomal PD-L1 (exoPD-L1) could induce immunosuppression functionally, thus impairing patients' survival in melanoma, NSCLC, and gastric cancer. However, no evidence demonstrates the feasibility of circulating exoPD-L1 and soluble PD-L1 (sPD-L1) as biomarkers for prognosis and early recurrence in colorectal liver metastasis (CRLM) patients following hepatectomy or their association with T cell infiltration at liver metastases. METHODS: In cohort 1, exoPD-L1 and sPD-L1 were preoperatively tested using ELISA. CD3, CD8, granzyme B (GB) and PD1 expressed at liver metastases were evaluated using immunohistochemistry. In cohort 2, exoPD-L1 and sPD-L1 were detected at baseline, before hepatectomy, after hepatectomy, and after disease progression. RESULTS: In cohort 1, higher preoperative exoPD-L1 or sPD-L1 significantly impaired RFS (exoPD-L1, P = 0.0043; sPD-L1, P = 0.0041) and OS (exoPD-L1, P = 0.0034; sPD-L1, P = 0.0061). Furthermore, preoperative exoPD-L1 was negatively correlated with CD3 + T-lymphocytes infiltrated at tumor center (CT), and GB and PD1 were expressed at tumor invasive margin (IM). Preoperative sPD-L1 was negatively correlated with CD3 + and CD8 + T-lymphocytes' infiltration at IM and CT, GB and PD1 expression at IM. In cohort 2, exoPD-L1 and sPD-L1 levels decreased following hepatectomy but increased when tumor progressed. Moreover, higher postoperative exoPD-L1 and sPD-L1 or a small reduction in exoPD-L1 and sPD-L1 levels after hepatectomy suggested higher early recurrence rate. CONCLUSIONS: Both preoperative exoPD-L1 and sPD-L1 had promising prognostic values and were associated with T cell infiltration at liver metastases in CRLM patients following hepatectomy. Dynamically tracking exoPD-L1 and sPD-L1 levels could monitor disease status and detect early recurrence.
Authors: Eddie K Abdalla; Jean-Nicolas Vauthey; Lee M Ellis; Vickie Ellis; Raphael Pollock; Kristine R Broglio; Kenneth Hess; Steven A Curley Journal: Ann Surg Date: 2004-06 Impact factor: 12.969
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