Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy

被引：323

作者：

Lee, Heng-Huan ^{[1
]}

Wang, Ying-Nai ^{[1
]}

Xia, Weiya ^{[1
]}

Chen, Chia-Hung ^{[2
,3
]}

Rau, Kun-Ming ^{[4
,5
]}

Ye, Leiguang ^{[6
]}

Wei, Yongkun ^{[1
]}

Chou, Chao-Kai ^{[1
]}

Wang, Shao-Chun ^{[7
,8
]}

Yan, Meisi ^{[1
,9
]}

Tu, Chih-Yen ^{[2
,3
]}

Hsia, Te-Chun ^{[2
,3
]}

Chiang, Shu-Fen ^{[10
]}

Chao, K. S. Clifford ^{[10
]}

Wistuba, Ignacio I. ^{[11
]}

Hsu, Jennifer L. ^{[1
,7
,8
,12
]}

Hortobagyi, Gabriel N. ^{[13
]}

Hung, Mien-Chie ^{[1
,7
,8
,12
,14
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[2] China Med Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Taichung 404, Taiwan

[3] China Med Univ, Sch Med, Taichung 404, Taiwan

[4] E Da Canc Hosp, Dept Hematol Oncol, Kaohsiung 824, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Kaohsiung 833, Taiwan

[6] Harbin Med Univ, Affiliated Tumor Hosp, Dept Pulm Oncol, Harbin 150081, Heilongjiang, Peoples R China

[7] China Med Univ, Grad Inst Biomed Sci, Taichung 404, Taiwan

[8] China Med Univ, Ctr Mol Med, Taichung 404, Taiwan

[9] Harbin Med Univ, Dept Pathol, Harbin 150081, Heilongjiang, Peoples R China

[10] China Med Univ, China Med Univ Hosp, Canc Ctr, Taichung 404, Taiwan

[11] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[12] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan

[13] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[14] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA

来源：

CANCER CELL | 2019年 / 36卷 / 02期

关键词：

CELL LUNG-CANCER; TUMOR-INFILTRATING LYMPHOCYTES; IMMUNE-CHECKPOINT BLOCKADE; PROGRAMMED DEATH LIGAND-1; STANDARDIZED METHOD; MASS-SPECTROMETRY; SOLID TUMORS; OPEN-LABEL; DOCETAXEL; BIOMARKERS;

D O I：

10.1016/j.ccell.2019.06.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.

引用

页码：168 / +

页数：15

共 42 条

[1] A review of guidelines for lung cancer [J].

Bironzo, Paolo ;

Di Maio, Massimo .

JOURNAL OF THORACIC DISEASE, 2018, 10 :S1556-S1563

[2] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[3] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[4] Patient selection for anti-PD-1/PD-L1 therapy in advanced non-small-cell lung cancer: implications for clinical practice [J].

Califano, Raffaele ;

Lal, Rohit ;

Lewanski, Conrad ;

Nicolson, Marianne C. ;

Ottensmeier, Christian H. ;

Popat, Sanjay ;

Hodgson, Matthew ;

Postmus, Pieter E. .

FUTURE ONCOLOGY, 2018, 14 (23) :2415-2431

[5] Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future [J].

Chen, Lieping ;

Han, Xue .

JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (09) :3384-3391

[6] A QUICKSCORE METHOD FOR IMMUNOHISTOCHEMICAL SEMIQUANTITATION - VALIDATION FOR ESTROGEN-RECEPTOR IN BREAST CARCINOMAS [J].

DETRE, S ;

JOTTI, GS ;

DOWSETT, M .

JOURNAL OF CLINICAL PATHOLOGY, 1995, 48 (09) :876-878

[7] Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma [J].

Eggermont, Alexander M. M. ;

Blank, Christian U. ;

Mandala, Mario ;

Long, Georgina, V ;

Atkinson, Victoria ;

Dalle, Stephane ;

Haydon, Andrew ;

Lichinitser, Mikhail ;

Khattak, Adnan ;

Carlino, Matteo S. ;

Sandhu, Shahneen ;

Larkin, James ;

Puig, Susana ;

Ascierto, Paolo A. ;

Rutkowski, Piotr ;

Schadendorf, Dirk ;

Koornstra, Rutger ;

Hernandez-Aya, Leonel ;

Maio, Michele ;

van den Eertwegh, Alfonsus J. M. ;

Grob, Jean-Jacques ;

Gutzmer, Ralf ;

Jamal, Rahima ;

Lorigan, Paul ;

Ibrahim, Nageatte ;

Marreaud, Sandrine ;

van Akkooi, Alexander C. J. ;

Suciu, Stefan ;

Robert, Caroline .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (19) :1789-1801

[8] Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial [J].

Fehrenbacher, Louis ;

Spira, Alexander ;

Ballinger, Marcus ;

Kowanetz, Marcin ;

Vansteenkiste, Johan ;

Mazieres, Julien ;

Park, Keunchil ;

Smith, David ;

Artal-Cortes, Angel ;

Lewanski, Conrad ;

Braiteh, Fadi ;

Waterkamp, Daniel ;

He, Pei ;

Zou, Wei ;

Chen, Daniel S. ;

Yi, Jing ;

Sandler, Alan ;

Rittmeyer, Achim .

LANCET, 2016, 387 (10030) :1837-1846

[9] Principles of Analytic Validation of Immunohistochemical Assays Guideline From the College of American Pathologists Pathology and Laboratory Quality Center [J].

Fitzgibbons, Patrick L. ;

Bradley, Linda A. ;

Fatheree, Lisa A. ;

Alsabeh, Randa ;

Fulton, Regan S. ;

Goldsmith, Jeffrey D. ;

Haas, Thomas S. ;

Karabakhtsian, Rouzan G. ;

Loykasek, Patti A. ;

Marolt, Monna J. ;

Shen, Steven S. ;

Smith, Anthony T. ;

Swanson, Paul E. .

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, 2014, 138 (11) :1432-1443

[10] Neoadjuvant PD-1 Blockade in Resectable Lung Cancer [J].

Forde, P. M. ;

Chaft, J. E. ;

Smith, K. N. ;

Anagnostou, V. ;

Cottrell, T. R. ;

Hellmann, M. D. ;

Zahurak, M. ;

Yang, S. C. ;

Jones, D. R. ;

Broderick, S. ;

Battafarano, R. J. ;

Velez, M. J. ;

Rekhtman, N. ;

Olah, Z. ;

Naidoo, J. ;

Marrone, K. A. ;

Verde, F. ;

Guo, H. ;

Zhang, J. ;

Caushi, J. X. ;

Chan, H. Y. ;

Sidhom, J. -W. ;

Scharpf, R. B. ;

White, J. ;

Gabrielson, E. ;

Wang, H. ;

Rosner, G. L. ;

Rusch, V. ;

Wolchok, J. D. ;

Merghoub, T. ;

Taube, J. M. ;

Velculescu, V. E. ;

Topalian, S. L. ;

Brahmer, J. R. ;

Pardoll, D. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (21) :1976-1986

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