Immunophenotypes of pancreatic ductal adenocarcinoma: Meta-analysis of transcriptional subtypes

被引：32

作者：

de Santiago, Ines ^{[1
]}

Yau, Christopher ^{[2
]}

Heij, Lara ^{[3
,4
]}

Middleton, Mark R. ^{[5
,6
]}

Markowetz, Florian ^{[1
]}

Grabsch, Heike, I ^{[3
,7
]}

Dustin, Michael L. ^{[8
,9
]}

Sivakumar, Shivan ^{[5
,8
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[2] Univ Birmingham, Ctr Computat Biol, Inst Canc & Genom Sci, Birmingham, W Midlands, England

[3] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Pathol, Med Ctr, Maastricht, Netherlands

[4] Univ Hosp RWTH Aachen, Dept Surg & Transplantat, Aachen, Germany

[5] Univ Oxford, Dept Oncol, Oxford, England

[6] Oxford Univ Hosp NHS Fdn Trust, OXford NIHR Biomed Res Ctr, Oxford, England

[7] Univ Leeds, Leeds Inst Med Res St Jamess, Div Pathol & Data Analyt, Leeds, W Yorkshire, England

[8] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[9] NYU, Sch Med, Dept Pathol, New York, NY USA

来源：

INTERNATIONAL JOURNAL OF CANCER | 2019年 / 145卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

pancreatic cancer; tumour microenvironment; T cells; adaptive immunity; innate immunity; subtypes; MUTATIONAL PROCESSES; METASTATIC MELANOMA; MOLECULAR SUBTYPES; ANALYSES REVEAL; CLASS DISCOVERY; PD-1; BLOCKADE; T-CELLS; TUMOR; SURVIVAL; INFILTRATION;

D O I：

10.1002/ijc.32186

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and has one of the highest mortality rates of any cancer type with a 5-year survival rate of <5%. Recent studies of PDAC have provided several transcriptomic classifications based on separate analyses of individual patient cohorts. There is a need to provide a unified transcriptomic PDAC classification driven by therapeutically relevant biologic rationale to inform future treatment strategies. Here, we used an integrative meta-analysis of 353 patients from four different studies to derive a PDAC classification based on immunologic parameters. This consensus clustering approach indicated transcriptomic signatures based on immune infiltrate classified as adaptive, innate and immune-exclusion subtypes. This reveals the existence of microenvironmental interpatient heterogeneity within PDAC and could serve to drive novel therapeutic strategies in PDAC including immune modulation approaches to treating this disease.

引用

页码：1125 / 1137

页数：13

共 57 条

[1] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2] Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study [J].

Ali, H. Raza ;

Chlon, Leon ;

Pharoah, Paul D. P. ;

Markowetz, Florian ;

Caldas, Carlos .

PLOS MEDICINE, 2016, 13 (12)

[3] Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy [J].

Angelova, Mihaela ;

Charoentong, Pornpimol ;

Hackl, Hubert ;

Fischer, Maria L. ;

Snajder, Rene ;

Krogsdam, Anne M. ;

Waldner, Maximilian J. ;

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Galon, Jerome ;

Trajanoski, Zlatko .

GENOME BIOLOGY, 2015, 16

[4]

[Anonymous], 2010, GENOME BIOL, DOI DOI 10.1186/gb-2010-11-10-r106

[5] xCell: digitally portraying the tissue cellular heterogeneity landscape [J].

Aran, Dvir ;

Hu, Zicheng ;

Butte, Atul J. .

GENOME BIOLOGY, 2017, 18

[6] Systematic pan-cancer analysis of tumour purity [J].

Aran, Dvir ;

Sirota, Marina ;

Butte, Atul J. .

NATURE COMMUNICATIONS, 2015, 6

[7] Genomic analyses identify molecular subtypes of pancreatic cancer [J].

Bailey, Peter ;

Chang, David K. ;

Nones, Katia ;

Johns, Amber L. ;

Patch, Ann-Marie ;

Gingras, Marie-Claude ;

Miller, David K. ;

Christ, Angelika N. ;

Bruxner, Tim J. C. ;

Quinn, Michael C. ;

Nourse, Craig ;

Murtaugh, L. Charles ;

Harliwong, Ivon ;

Idrisoglu, Senel ;

Manning, Suzanne ;

Nourbakhsh, Ehsan ;

Wani, Shivangi ;

Fink, Lynn ;

Holmes, Oliver ;

Chin, Vencssa ;

Anderson, Matthew J. ;

Kazakoff, Stephen ;

Leonard, Conrad ;

Newell, Felicity ;

Waddell, Nick ;

Wood, Scott ;

Xu, Qinying ;

Wilson, Peter J. ;

Cloonan, Nicole ;

Kassahn, Karin S. ;

Taylor, Darrin ;

Quek, Kelly ;

Robertson, Alan ;

Pantano, Lorena ;

Mincarelli, Laura ;

Sanchez, Luis N. ;

Evers, Lisa ;

Wu, Jianmin ;

Pinese, Mark ;

Cowley, Mark J. ;

Jones, Marc D. ;

Colvin, Emily K. ;

Nagrial, Adnan M. ;

Humphrey, Emily S. ;

Chantrill, Lorraine A. ;

Mawson, Amanda ;

Humphris, Jeremy ;

Chou, Angela ;

Pajic, Marina ;

Scarlett, Christopher J. .

NATURE, 2016, 531 (7592) :47-+

[8] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[9] Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Waldner, Maximilian ;

Obenauf, Anna C. ;

Angell, Helen ;

Fredriksen, Tessa ;

Lafontaine, Lucie ;

Berger, Anne ;

Bruneval, Patrick ;

Fridman, Wolf Herman ;

Becker, Christoph ;

Pages, Franck ;

Speicher, Michael R. ;

Trajanoski, Zlatko ;

Galon, Jerome .

IMMUNITY, 2013, 39 (04) :782-795

[10] Validation and comparison of the molecular classifications of pancreatic carcinomas [J].

Birnbaum, David J. ;

Finetti, Pascal ;

Birnbaum, Daniel ;

Mamessier, Emilie ;

Bertucci, Francois .

MOLECULAR CANCER, 2017, 16

← 1 2 3 4 5 6 →