PD-L1 expression on stromal tumor-infiltrating lymphocytes is a favorable prognostic factor in ovarian serous carcinoma

被引:32
作者
Kim, Ki Hyung [1 ]
Choi, Kyung Un [2 ]
Kim, Ahrong [2 ]
Lee, So Jung [2 ]
Lee, Jung Hee [3 ,4 ]
Suh, Dong Soo [1 ]
Kwon, Byung-su [1 ]
Hwang, Chungsu [3 ,4 ]
机构
[1] Pusan Natl Univ Hosp, Dept Obstet & Gynecol, 179 Gudeok Ro, Busan 49241, South Korea
[2] Pusan Natl Univ Hosp, Dept Pathol, 179 Gudeok Ro, Busan 49241, South Korea
[3] Pusan Natl Univ, Yangsan Hosp, Dept Pathol, 20,Geumo Ro, Yangsan Si, Gyeongsangnam D, South Korea
[4] Res Inst Convergence Biomed Sci & Technol, 20,Geumo Ro, Yangsan Si, Gyeongsangnam D, South Korea
关键词
Ovarian cancer; Tumor-infiltrating lymphocyte; PD-L1; Survival; T-CELLS; GRADE; OVEREXPRESSION; IMPACT;
D O I
10.1186/s13048-019-0526-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
BackgroundPD-L1 expression levels determined by immunostaining are known to be related to the survival rate and prognosis of patients with various types of cancers, as well as to the therapeutic response to immune checkpoint inhibitors. Recently, the U.S. Food and Drug Administration approved an immune checkpoint inhibitor for the treatment of non-small cell lung cancer along with the clones used for PD-L1 immunostaining to predict the resulting response. In this study, we performed PD-L1 immunostaining of tissue microarrays from ovarian epithelial cancer using SP263, an approved clone, and examined the effect of PD-L1 expression on survival rate and prognosis.MethodsTissue microarrays were constructed from ovarian epithelial cancer tissues of 248 patients and PD-L1 immunostaining was performed using the SP263 clone. PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were evaluated, and the effect of PD-L1 expression on survival and prognosis was analyzed.ResultsPD-L1 was detected in tumor cells as well as intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. It was most frequently expressed in stromal tumor-infiltrating lymphocytes. The Kaplan-Meier curve analysis and log rank test showed that only high stromal PD-L1 expression was associated with increased overall survival in ovarian serous carcinoma. Multivariate and univariate Cox regression analyses revealed that stromal PD-L1 expression was an independent prognostic factor, especially in ovarian serous carcinoma.ConclusionsPD-L1 immunostaining using SP263 was observed in tumor cells as well as intraepithelial and stromal tumor-infiltrating lymphocytes. PD-L1-expressing stromal tumor-infiltrating lymphocytes were associated with an increased overall survival rate and may serve as a favorable prognostic factor in ovarian cancer, particularly serous carcinoma.
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共 21 条
[1]   Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer [J].
Aust, Stefanie ;
Felix, Sophie ;
Auer, Katharina ;
Bachmayr-Heyda, Anna ;
Kenner, Lukas ;
Dekan, Sabine ;
Meier, Samuel M. ;
Gerner, Christopher ;
Grimm, Christoph ;
Pils, Dietmar .
SCIENTIFIC REPORTS, 2017, 7
[2]   Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment [J].
Chanmee, Theerawut ;
Ontong, Pawared ;
Konno, Kenjiro ;
Itano, Naoki .
CANCERS, 2014, 6 (03) :1670-1690
[3]   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
[4]  
Dong H, 2002, NAT REV IMMUNOL, V2, P545, DOI 10.1038/nm730
[5]   Clinical impact of programmed cell death ligand 1 expression in colorectal cancer [J].
Droeser, Raoul A. ;
Hirt, Christian ;
Viehl, Carsten T. ;
Frey, Daniel M. ;
Nebiker, Christian ;
Huber, Xaver ;
Zlobec, Inti ;
Eppenberger-Castori, Serenella ;
Tzankov, Alexander ;
Rosso, Raffaele ;
Zuber, Markus ;
Muraro, Manuele Giuseppe ;
Amicarella, Francesca ;
Cremonesi, Eleonora ;
Heberer, Michael ;
Iezzi, Giandomenica ;
Lugli, Alessandro ;
Terracciano, Luigi ;
Sconocchia, Giuseppe ;
Oertli, Daniel ;
Spagnoli, Giulio C. ;
Tornillo, Luigi .
EUROPEAN JOURNAL OF CANCER, 2013, 49 (09) :2233-2242
[6]   Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma [J].
Gao, Qiang ;
Wang, Xiao-Ying ;
Qiu, Shuang-Jian ;
Yamato, Ichiro ;
Sho, Masayuki ;
Nakajima, Yoshiyuki ;
Zhou, Jian ;
Li, Bai-Zhou ;
Shi, Ying-Hong ;
Xiao, Yong-Sheng ;
Xu, Yang ;
Fan, Jia .
CLINICAL CANCER RESEARCH, 2009, 15 (03) :971-979
[7]   Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].
Garon, Edward B. ;
Rizvi, Naiyer A. ;
Hui, Rina ;
Leighl, Natasha ;
Balmanoukian, Ani S. ;
Eder, Joseph Paul ;
Patnaik, Amita ;
Aggarwal, Charu ;
Gubens, Matthew ;
Horn, Leora ;
Carcereny, Enric ;
Ahn, Myung-Ju ;
Felip, Enriqueta ;
Lee, Jong-Seok ;
Hellmann, Matthew D. ;
Hamid, Omid ;
Goldman, Jonathan W. ;
Soria, Jean-Charles ;
Dolled-Filhart, Marisa ;
Rutledge, Ruth Z. ;
Zhang, Jin ;
Lunceford, Jared K. ;
Rangwala, Reshma ;
Lubiniecki, Gregory M. ;
Roach, Charlotte ;
Emancipator, Kenneth ;
Gandhi, Leena .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028
[8]   Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer [J].
Hamanishi, Junzo ;
Mandai, Masaki ;
Iwasaki, Masashi ;
Okazaki, Taku ;
Tanaka, Yoshimasa ;
Yamaguchi, Ken ;
Higuchi, Toshihiro ;
Yagi, Haruhiko ;
Takakura, Kenji ;
Minato, Nagahiro ;
Honjo, Tasuku ;
Fujii, Shingo .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (09) :3360-3365
[9]   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-+
[10]   Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade [J].
Iwai, Y ;
Ishida, M ;
Tanaka, Y ;
Okazaki, T ;
Honjo, T ;
Minato, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (19) :12293-12297