Annals of surgical oncology · 2016
Program Death 1 Immune Checkpoint and Tumor Microenvironment: Implications for Patients With Intrahepatic Cholangiocarcinoma.
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Gani Faiz, Nagarajan Neeraja, Kim Yuhree, Zhu Qingfeng, Luan Lan, Bhaijjee Feriyl, Anders Robert A, Pawlik Timothy M
Аннотация
BACKGROUND: Program death 1 (PD-1) and its ligand (PD-L1) have been identified as potential therapeutic targets for solid and hematologic malignancies. The current study aimed to assess PD-L1 expression in intrahepatic cholangiocarcinoma (ICC) and relate clinical outcomes to its expression.
METHODS: Formalin-fixed, paraffin-embedded tumor specimens were obtained for patients undergoing surgery at Johns Hopkins Hospital between 1991 and 2011. Immunohistochemistry was used to assess PD-L1 expression in tumor-associated macrophages (TAMs) and within the tumor front (TF).
RESULTS: Of 54 tumor samples analyzed, 34 stained positive for PD-L1 expression on TAMs (TAMs+), and 39 stained positive for PD-L1 expression on cells within the tumor front (TF+). The TF+ patients were less likely to present with metastatic lymph nodes (N1 patients: 26.7 vs 7.7 %; p = 0.011), whereas all tumors with intrahepatic metastasis failed to demonstrate staining for PD-L1 around the tumor front (p = 0.020). Patients with tumors shown to be TAMs+ were less likely to present with multiple lesions (35.0 vs 8.8 %; p = 0.017). Patients with tumors exhibiting PD-L1 expression around the tumor front demonstrated a worse overall survival than TF patients (p = 0.008). Multivariable analysis showed that patients with tumors staining for PD-L1 in the tumor front had a 59.5 % reduced survival (TF- vs TF+: time ratio, 0.405; 95 % confidence interval, 0.215-0.761; p = 0.005).
CONCLUSION: Expression of PD-L1 was noted among a majority of patients, and PD-L1 expression within the tumor front was associated with a 60 % decreased survival. Future clinical trials are necessary to assess the safety and efficacy of anti-PD-L1 therapies among patients with ICC.
METHODS: Formalin-fixed, paraffin-embedded tumor specimens were obtained for patients undergoing surgery at Johns Hopkins Hospital between 1991 and 2011. Immunohistochemistry was used to assess PD-L1 expression in tumor-associated macrophages (TAMs) and within the tumor front (TF).
RESULTS: Of 54 tumor samples analyzed, 34 stained positive for PD-L1 expression on TAMs (TAMs+), and 39 stained positive for PD-L1 expression on cells within the tumor front (TF+). The TF+ patients were less likely to present with metastatic lymph nodes (N1 patients: 26.7 vs 7.7 %; p = 0.011), whereas all tumors with intrahepatic metastasis failed to demonstrate staining for PD-L1 around the tumor front (p = 0.020). Patients with tumors shown to be TAMs+ were less likely to present with multiple lesions (35.0 vs 8.8 %; p = 0.017). Patients with tumors exhibiting PD-L1 expression around the tumor front demonstrated a worse overall survival than TF patients (p = 0.008). Multivariable analysis showed that patients with tumors staining for PD-L1 in the tumor front had a 59.5 % reduced survival (TF- vs TF+: time ratio, 0.405; 95 % confidence interval, 0.215-0.761; p = 0.005).
CONCLUSION: Expression of PD-L1 was noted among a majority of patients, and PD-L1 expression within the tumor front was associated with a 60 % decreased survival. Future clinical trials are necessary to assess the safety and efficacy of anti-PD-L1 therapies among patients with ICC.