Immunogenomic Landscape of Hematological Malignancies

被引：120

作者：

Dufva, Olli ^{[1
,2
,3
,4
]}

Polonen, Petri ^{[5
]}

Bruck, Oscar ^{[1
,2
,3
,4
]}

Keranen, Mikko Ai ^{[1
,2
,3
]}

Klievink, Jay ^{[1
,2
,3
]}

Mehtonen, Juha ^{[5
]}

Huuhtanen, Jani ^{[1
,2
,3
]}

Kumar, Ashwini ^{[6
]}

Malani, Disha ^{[6
]}

Siitonen, Sanna ^{[7
]}

Kankainen, Matti ^{[1
,2
,3
,4
]}

Ghimire, Bishwa ^{[6
]}

Lahtela, Jenni ^{[6
]}

Mattila, Pirkko ^{[6
]}

Vaha-Koskela, Markus ^{[6
]}

Wennerberg, Krister ^{[6
]}

Granberg, Kirsi ^{[8
]}

Leivonen, Suvi-Katri ^{[9
,10
]}

Meriranta, Leo ^{[9
,10
]}

Heckman, Caroline ^{[4
,6
]}

Leppa, Sirpa ^{[4
,9
,10
]}

Nykter, Matti ^{[8
]}

Lohi, Olli ^{[11
]}

Heinaniemi, Merja ^{[5
]}

Mustjoki, Satu ^{[1
,2
,3
,4
]}

机构：

[1] Univ Helsinki, Hosp Comprehens Canc Ctr HUH CCC, Hematol Res Unit Helsinki, Helsinki 00029, Finland

[2] Univ Helsinki UH, Translat Immunol Res Program, Helsinki 00029, Finland

[3] Univ Helsinki UH, Dept Clin Chem & Hematol, Helsinki 00029, Finland

[4] iCAN Digital Precis Canc Med Flagship, Helsinki, Finland

[5] Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio 70211, Finland

[6] Inst Mol Med Finland, UH, Helsinki 00014, Finland

[7] UH & HUSLAB, Dept Clin Chem, HUH, Helsinki 00029, Finland

[8] Tampere Univ TU, Fac Med & Hlth Technol, Lab Computat Biol, Tampere 33014, Finland

[9] HUH CCC, Dept Oncol, Helsinki 00029, Finland

[10] Fac Med, Appl Tumor Genom Res Program, UH, Helsinki 00014, Finland

[11] Tampere Univ Hosp, Tampere Ctr Child Hlth Res, TU & Tays Canc Ctr, Tampere 33521, Finland

来源：

CANCER CELL | 2020年 / 38卷 / 03期

基金：

芬兰科学院;

关键词：

CANCER-TESTIS ANTIGENS; CLASS-II EXPRESSION; COMPLEX CLASS-II; IMMUNE LANDSCAPE; GENE-EXPRESSION; TUMOR MICROENVIRONMENT; MULTIPLE-MYELOMA; INTERFERON-GAMMA; DNA METHYLATION; PD-1; BLOCKADE;

D O I：

10.1016/j.ccell.2020.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-gamma response in lymphoma. CIITA methylation regulating antigen presentation, cancer type-specific immune checkpoints, such as VISTA in myeloid malignancies, and variation in cancer antigen expression further contributed to immune heterogeneity and predicted survival. Our study provides a resource linking immunology with cancer subtypes and genomics in hematological malignancies.

引用

页码：380 / +

页数：33

共 130 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] CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens [J].

Almeida, Luiz Gonzaga ;

Sakabe, Noboru J. ;

deOliveira, Alice R. ;

Silva, Maria Cristina C. ;

Mundstein, Alex S. ;

Cohen, Tzeela ;

Chen, Yao-Tseng ;

Chua, Ramon ;

Gurung, Sita ;

Gnjatic, Sacha ;

Jungbluth, Achim A. ;

Caballero, Otavia L. ;

Bairoch, Amos ;

Kiesler, Eva ;

White, Sarah L. ;

Simpson, Andrew J. G. ;

Old, Lloyd J. ;

Camargo, Anamaria A. ;

Vasconcelos, Ana Tereza R. .

NUCLEIC ACIDS RESEARCH, 2009, 37 :D816-D819

[3] Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study [J].

Ansell, Stephen M. ;

Minnema, Monique C. ;

Johnson, Peter ;

Timmerman, John M. ;

Armand, Philippe ;

Shipp, Margaret A. ;

Rodig, Scott J. ;

Ligon, Azra H. ;

Roemer, Margaretha G. M. ;

Reddy, Nishitha ;

Cohen, Jonathon B. ;

Assouline, Sarit ;

Poon, Michelle ;

Sharma, Manish ;

Kato, Kazunobu ;

Samakoglu, Selda ;

Sumbul, Anne ;

Grigg, Andrew .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (06) :481-+

[4] PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].

Ansell, Stephen M. ;

Lesokhin, Alexander M. ;

Borrello, Ivan ;

Halwani, Ahmad ;

Scott, Emma C. ;

Gutierrez, Martin ;

Schuster, Stephen J. ;

Millenson, Michael M. ;

Cattry, Deepika ;

Freeman, Gordon J. ;

Rodig, Scott J. ;

Chapuy, Bjoern ;

Ligon, Azra H. ;

Zhu, Lili ;

Grosso, Joseph F. ;

Kim, Su Young ;

Timmerman, John M. ;

Shipp, Margaret A. ;

Armand, Philippe .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319

[5] Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage [J].

Aran, Dvir ;

Looney, Agnieszka P. ;

Liu, Leqian ;

Wu, Esther ;

Fong, Valerie ;

Hsu, Austin ;

Chak, Suzanna ;

Naikawadi, Ram P. ;

Wolters, Paul J. ;

Abate, Adam R. ;

Butte, Atul J. ;

Bhattacharya, Mallar .

NATURE IMMUNOLOGY, 2019, 20 (02) :163-+

[6] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[7] Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation [J].

Atanackovic, Djordje ;

Arfsten, Julia ;

Cao, Yanran ;

Gnjatic, Sacha ;

Schnieders, Frank ;

Bartels, Katrin ;

Schilling, Georgia ;

Faltz, Christiane ;

Wolschke, Christine ;

Dierlamm, Judith ;

Ritter, Gerd ;

Eiermann, Thomas ;

Hossfeld, Dieter Kurt ;

Zander, Axel R. ;

Jungbluth, Achim A. ;

Old, Lloyd J. ;

Bokemeyer, Carsten ;

Kroeger, Nicolaus .

BLOOD, 2007, 109 (03) :1103-1112

[8] IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade [J].

Ayers, Mark ;

Lunceford, Jared ;

Nebozhyn, Michael ;

Murphy, Erin ;

Loboda, Andrey ;

Kaufman, David R. ;

Albright, Andrew ;

Cheng, Jonathan D. ;

Kang, S. Peter ;

Shankaran, Veena ;

Piha-Paul, Sarina A. ;

Yearley, Jennifer ;

Seiwert, Tanguy Y. ;

Ribas, Antoni ;

McClanahan, Terrill K. .

JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (08) :2930-2940

[9] Haematological malignancies: at the forefront of immunotherapeutic innovation [J].

Bachireddy, Pavan ;

Burkhardt, Ute E. ;

Rajasagi, Mohini ;

Wu, Catherine J. .

NATURE REVIEWS CANCER, 2015, 15 (04) :201-215

[10] The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

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