Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy

被引：113

作者：

Riaz, Nadeem ^{[1
,2
,3
]}

Havel, Jonathan J. ^{[1
]}

Kendall, Sviatoslav M. ^{[1
]}

Makarov, Vladimir ^{[1
]}

Walsh, Logan A. ^{[1
]}

Desrichard, Alexis ^{[1
]}

Weinhold, Nils ^{[2
]}

Chan, Timothy A. ^{[1
,2
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Immunogen & Precis Oncol Platform, 1275 York Ave, New York, NY 10021 USA

来源：

NATURE GENETICS | 2016年 / 48卷 / 11期

关键词：

CTLA-4; BLOCKADE; PD-1; CELL; NIVOLUMAB; SENSITIVITY;

D O I：

10.1038/ng.3677

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Immune checkpoint blockade has shown significant promise as an anticancer treatment, yet the determinants of response are not completely understood. Here we show that somatic mutations in SERPINB3 and SERPINB4 are associated with survival after anti-CTLA4 immunotherapy in two independent cohorts of patients with melanoma (n = 174). Interestingly, serpins are homologs of the well-known ovalbumin antigen and are associated with autoimmunity. Our findings have implications for the personalization of immunotherapy.

引用

页码：1327 / 1329

页数：3

共 24 条

[1] Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[2] 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

[3] Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4 [J].

Catanzaro, Joseph M. ;

Sheshadri, Namratha ;

Pan, Ji-An ;

Sun, Yu ;

Shi, Chanjuan ;

Li, Jinyu ;

Powers, R. Scott ;

Crawford, Howard C. ;

Zong, Wei-Xing .

NATURE COMMUNICATIONS, 2014, 5

[4] Humoral autoimmune responses to the squamous cell carcinoma antigen protein family in psoriasis [J].

El-Rachkidy, Rana G. ;

Young, Helen S. ;

Griffiths, Christopher F. M. ;

Camp, Richard D. R. .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2008, 128 (09) :2219-2224

[5] Serpins, Immunity and Autoimmunity: Old Molecules, New Functions [J].

Gatto, Mariele ;

Iaccarino, Luca ;

Ghirardello, Anna ;

Bassi, Nicola ;

Pontisso, Patrizia ;

Punzi, Leonardo ;

Shoenfeld, Yehuda ;

Doria, Andrea .

CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2013, 45 (02) :267-280

[6] Cancer systems biology of TCGA SKCM: Efficient detection of genomic drivers in melanoma [J].

Guan, Jian ;

Gupta, Rohit ;

Filipp, Fabian V. .

SCIENTIFIC REPORTS, 2015, 5

[7] Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [J].

Hodi, F. Stephen ;

O'Day, Steven J. ;

McDermott, David F. ;

Weber, Robert W. ;

Sosman, Jeffrey A. ;

Haanen, John B. ;

Gonzalez, Rene ;

Robert, Caroline ;

Schadendorf, Dirk ;

Hassel, Jessica C. ;

Akerley, Wallace ;

van den Eertwegh, Alfons J. M. ;

Lutzky, Jose ;

Lorigan, Paul ;

Vaubel, Julia M. ;

Linette, Gerald P. ;

Hogg, David ;

Ottensmeier, Christian H. ;

Lebbe, Celeste ;

Peschel, Christian ;

Quirt, Ian ;

Clark, Joseph I. ;

Wolchok, Jedd D. ;

Weber, Jeffrey S. ;

Tian, Jason ;

Yellin, Michael J. ;

Nichol, Geoffrey M. ;

Hoos, Axel ;

Urba, Walter J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (08) :711-723

[8] Specific T cell lines for ovalbumin, ovomucoid, lysozyme and two OA synthetic epitopes, generated from egg allergic patients' PBMC [J].

Holen, E ;

Elsayed, S .

CLINICAL AND EXPERIMENTAL ALLERGY, 1996, 26 (09) :1080-1088

[9] Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH2-terminal kinase [J].

Katagiri, C ;

Nakanishi, J ;

Kadoya, K ;

Hibino, T .

JOURNAL OF CELL BIOLOGY, 2006, 172 (07) :983-990

[10] PD-1 Blockade in Tumors with Mismatch-Repair Deficiency [J].

Le, D. T. ;

Uram, J. N. ;

Wang, H. ;

Bartlett, B. R. ;

Kemberling, H. ;

Eyring, A. D. ;

Skora, A. D. ;

Luber, B. S. ;

Azad, N. S. ;

Laheru, D. ;

Biedrzycki, B. ;

Donehower, R. C. ;

Zaheer, A. ;

Fisher, G. A. ;

Crocenzi, T. S. ;

Lee, J. J. ;

Duffy, S. M. ;

Goldberg, R. M. ;

de la Chapelle, A. ;

Koshiji, M. ;

Bhaijee, F. ;

Huebner, T. ;

Hruban, R. H. ;

Wood, L. D. ;

Cuka, N. ;

Pardoll, D. M. ;

Papadopoulos, N. ;

Kinzler, K. W. ;

Zhou, S. ;

Cornish, T. C. ;

Taube, J. M. ;

Anders, R. A. ;

Eshleman, J. R. ;

Vogelstein, B. ;

Diaz, L. A., Jr. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2509-2520

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