PD-L1 expression in extrahepatic cholangiocarcinoma

被引:70
作者
Walter, Dirk [1 ,2 ]
Herrmann, Eva [3 ]
Schnitzbauer, Andreas A. [4 ]
Zeuzem, Stefan [1 ]
Hansmann, Martin Leo [2 ]
Peveling-Oberhag, Jan [1 ,2 ,5 ]
Hartmann, Sylvia [2 ]
机构
[1] Johann Wolfgang Goethe Univ Hosp, Dept Internal Med 1, Theodor Stern Kai 7, D-60590 Frankfurt, Germany
[2] Johann Wolfgang Goethe Univ Hosp, Dr Senckenberg Inst Pathol, Frankfurt, Germany
[3] Johann Wolfgang Goethe Univ Hosp, Inst Biostat & Math Modelling, Frankfurt, Germany
[4] Johann Wolfgang Goethe Univ Hosp, Dept Gen & Visceral Surg, Frankfurt, Germany
[5] Robert Bosch Krankenhaus, Dept Gastroenterol Hepatol & Endocrinol, Stuttgart, Germany
关键词
extrahepatic cholangiocarcinoma; PD-1; PD-L1; tumour-associated macrophages; tumour-infiltrating lymphocytes; LIGAND; 1; PD-L1; CLINICAL-SIGNIFICANCE; ANTI-PD-L1; ANTIBODY; PROGNOSTIC IMPACT; T-CELLS; TUMOR; CARCINOMA; MPDL3280A; PATHWAY; SAFETY;
D O I
10.1111/his.13238
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
AimsTo investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). Methods and resultsTissue samples from patients with eCCA [n=69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined. PD-L1 was found on both tumour cells of eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant correlations of PD-L1 expression on cancer cells with venous invasion (P=0.031) and poor differentiation of the tumour (P=0.048) were observed. In 19 of 69 (27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas infiltration with CD3-positive and CD163-positive cells was found in 63 of 69 (91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five CD3-positive cells per high-power field was significantly correlated with poorer differentiation (P=0.015) and venous invasion (P<0.001) of CCA. PD-L1 expression was not correlated with patient survival, but PD-L1 expression on tumour cells combined with low infiltration of CD3-positive TILs was associated with an unfavourable outcome (P=0.027). ConclusionOnly a small number of eCCA patients are PD-L1-positive, which might be important for future application of PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more invasive growth and worse overall survival.
引用
收藏
页码:383 / 392
页数:10
相关论文
共 28 条
[1]   Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired [J].
Ahmadzadeh, Mojgan ;
Johnson, Laura A. ;
Heemskerk, Bianca ;
Wunderlich, John R. ;
Dudley, Mark E. ;
White, Donald E. ;
Rosenberg, Steven A. .
BLOOD, 2009, 114 (08) :1537-1544
[2]   Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma [J].
Bellmunt, J. ;
Mullane, S. A. ;
Werner, L. ;
Fay, A. P. ;
Callea, M. ;
Leow, J. J. ;
Taplin, M. E. ;
Choueiri, T. K. ;
Hodi, F. S. ;
Freeman, G. J. ;
Signoretti, S. .
ANNALS OF ONCOLOGY, 2015, 26 (04) :812-817
[3]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[4]   Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies [J].
Brandi, Giovanni ;
Farioli, Andrea ;
Astolfi, Annalisa ;
Biasco, Guido ;
Tavolari, Simona .
ONCOTARGET, 2015, 6 (17) :14744-14753
[5]   Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma [J].
Darb-Esfahani, Silvia ;
Kunze, Catarina Alisa ;
Kulbe, Hagen ;
Sehouli, Jalid ;
Wienert, Stephan ;
Lindner, Judith ;
Budczies, Jan ;
Bockmayr, Michael ;
Dietel, Manfred ;
Denkert, Carsten ;
Braicu, Ioana ;
Joehrens, Korinna .
ONCOTARGET, 2016, 7 (02) :1486-1499
[6]   Cholangiocarcinoma - Thirty-one-year experience with 564 patients at a single institution [J].
DeOliveira, Michelle L. ;
Cunningham, Steven C. ;
Cameron, John L. ;
Kamangar, Farin ;
Winter, Jordan M. ;
Lillemoe, Keith D. ;
Choti, Michael C. ;
Yeo, Charles J. ;
Schulick, Richard D. .
ANNALS OF SURGERY, 2007, 245 (05) :755-762
[7]  
Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
[8]   Program Death 1 Immune Checkpoint and Tumor Microenvironment: Implications for Patients With Intrahepatic Cholangiocarcinoma [J].
Gani, Faiz ;
Nagarajan, Neeraja ;
Kim, Yuhree ;
Zhu, Qingfeng ;
Luan, Lan ;
Bhaijjee, Feriyl ;
Anders, Robert A. ;
Pawlik, Timothy M. .
ANNALS OF SURGICAL ONCOLOGY, 2016, 23 (08) :2610-2617
[9]   Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma [J].
Hasita, Horlad ;
Komohara, Yoshihiro ;
Okabe, Hirohisa ;
Masuda, Toshiro ;
Ohnishi, Koji ;
Lei, Xiao F. ;
Beppu, Toru ;
Baba, Hideo ;
Takeya, Motohiro .
CANCER SCIENCE, 2010, 101 (08) :1913-1919
[10]   Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients [J].
Herbst, Roy S. ;
Soria, Jean-Charles ;
Kowanetz, Marcin ;
Fine, Gregg D. ;
Hamid, Omid ;
Gordon, Michael S. ;
Sosman, Jeffery A. ;
McDermott, David F. ;
Powderly, John D. ;
Gettinger, Scott N. ;
Kohrt, Holbrook E. K. ;
Horn, Leora ;
Lawrence, Donald P. ;
Rost, Sandra ;
Leabman, Maya ;
Xiao, Yuanyuan ;
Mokatrin, Ahmad ;
Koeppen, Hartmut ;
Hegde, Priti S. ;
Mellman, Ira ;
Chen, Daniel S. ;
Hodi, F. Stephen .
NATURE, 2014, 515 (7528) :563-+