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Distinct PD-L1/PD1 Profiles and Clinical Implications in Intrahepatic Cholangiocarcinoma Patients with Different Risk Factors

Article scientifique 2019 Anglais

Résumé

Rationale: PD1/PD-L1 immune checkpoint inhibitors have shown promising results for several malignancies. However, PD1/PD-L1 signaling and its therapeutic significance remains largely unknown in intrahepatic cholangiocarcinoma (ICC) cases with complex etiology. Methods: We investigated the expression and clinical significance of CD3 and PD1/PD-L1 in 320 ICC patients with different risk factors. In addition, we retrospectively analyzed 7 advanced ICC patients who were treated with PD1 inhibitor. Results: The cohort comprised 233 patients with HBV infection, 18 patients with hepatolithiasis, and 76 patients with undetermined risk factors. PD-L1 was mainly expressed in tumor cells, while CD3 and PD1 were expressed in infiltrating lymphocytes of tumor tissues. PD1/PD-L1 signals were activated in tumor tissues, and expression was positively correlated with HBV infection and lymph node invasion. More PD1 + T cells and higher PD-L1 expression were observed in tumor tissues of ICC patients with HBV infection compared to patients with hepatolithiasis or undetermined risk factors. More PD1 + T cells and/or high PD-L1 expression negatively impacted the prognosis of patients with HBV infection but not those with hepatolithiasis. Multivariate analysis showed PD1/PD-L1 expression was an independent indicator of ICC patient prognosis. Advanced ICC patients with HBV infection and less PD1 + T cells tended to have good response to anti-PD1 therapy. Conclusion: Hyperactivated PD1/PD-L1 signals in tumor tissues are a negative prognostic marker for ICCs after resection. HBV infection-and hepatolithiasis-related ICCs have distinct PD1/PD-L1 profiles. Further, PD1 + T cells could be used as a biomarker to predict prognosis and assay the efficiency of anti-PD1 immunotherapy in ICC patients with HBV infection.

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Lu, J., Zeng, H., Sun, Q., Meng, Q., Huang, X., Zhang, P., Yang, X., Peng, R., Gao, C., Wei, C., Shen, Y., Cai, J., Dong, R., Shi, Y., Sun, H., Shi, Y., Zhou, J., Fan, J., Ke, A., Yang, L., Shi, G. (2019). Distinct PD-L1/PD1 Profiles and Clinical Implications in Intrahepatic Cholangiocarcinoma Patients with Different Risk Factors. https://doi.org/10.7150/thno.36276

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Auteur(s)

Jia‐Cheng Lu Haiying Zeng Qi‐Man Sun Qingnan Meng Xiaoyong Huang Pengfei Zhang Xuan Yang Rui Peng Chao Gao Chuanyuan Wei Ying‐Hao Shen Jia-Bing Cai Rui‐Zhao Dong Ying–Hong Shi Hui‐Chuan Sun Yujiang Geno Shi Jian Zhou Jia Fan Ai‐Wu Ke Liu‐Xiao Yang Guo‐Ming Shi

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