Expand to shield: IL-15 and in situ lymphocytic proliferation

被引:6
作者
Bindea, Gabriela [1 ,2 ,3 ]
Mlecnik, Bernhard [1 ,2 ,3 ,4 ]
Galon, Jerome [1 ,2 ,3 ]
机构
[1] INSERM, Lab Integrat Canc Immunol, Paris, France
[2] Equipe Labellisee Ligue Canc, Paris, France
[3] Univ Paris, Sorbonne Univ, Ctr Rech Cordeliers, Paris, France
[4] Inovarion, Paris, France
关键词
T-cells; proliferation; attraction; IL-15; chemokine; chromosomal instability; tumor microenvironment; colorectal cancer; prognosis; survival; immunity; immunoscore;
D O I
10.1080/2162402X.2021.1886726
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The tumor microenvironment includes a complex network of cytokines and chemokines that contribute to shaping the intratumoral immune reaction. Understanding the mechanisms leading to immune-hot (Immunoscore-high) altered (excluded and immunosuppressed) and cold tumors are of critical importance for successful anti-cancer therapies. Two essential mechanisms are highlighted. Specific chemokines and adhesion molecules appeared to target and attract immune effector T cells to the tumor microenvironment and to specific regions within the tumor. These mechanisms are dependent upon intratumoral IL-15 expression. Decreased IL15 expression also affected the local proliferation of B and T lymphocytes. A comprehensive analysis revealed a major contribution of IL15 in shaping the tumor immune contexture. Thus, an in situ lymphocytic infiltration is mediated through chemokines and attraction inside or around the tumor microenvironment, and an IL15-mediated in situ lymphocytic proliferation, which expand the local pool of intratumoral cytotoxic CD8 T-cells are key determinants of the immune contexture. Increased IL15 expression and local proliferation of T-cells were associated with decreased risk of tumor recurrence and prolonged survival of cancer patients. These data provide further mechanisms to prioritize research and help in designing better therapeutic interventions.
引用
收藏
页数:3
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共 16 条
[1]   Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10 [J].
Bergamaschi, Cristina ;
Pandit, Hrishikesh ;
Nagy, Bethany A. ;
Stellas, Dimitris ;
Jensen, Shawn M. ;
Bear, Jenifer ;
Cam, Maggie ;
Valentin, Antonio ;
Fox, Bernard A. ;
Felber, Barbara K. ;
Pavlakis, George N. .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
[2]   The prognostic impact of anti-cancer immune response: a novel classification of cancer patients [J].
Bindea, Gabriela ;
Mlecnik, Bernhard ;
Fridman, Wolf-Herman ;
Galon, Jerome .
SEMINARS IN IMMUNOPATHOLOGY, 2011, 33 (04) :335-340
[3]   The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy [J].
Bruni, Daniela ;
Angell, Helen K. ;
Galon, Jerome .
NATURE REVIEWS CANCER, 2020, 20 (11) :662-680
[4]   Immunoscore and Immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015 [J].
Galon, J. ;
Fox, B. A. ;
Bifulco, C. B. ;
Masucci, G. ;
Rau, T. ;
Botti, G. ;
Marincola, F. M. ;
Ciliberto, G. ;
Pages, F. ;
Ascierto, P. A. ;
Capone, M. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2016, 14
[5]   Tumor Immunology and Tumor Evolution: Intertwined Histories [J].
Galon, Jerome ;
Bruni, Daniela .
IMMUNITY, 2020, 52 (01) :55-81
[6]   Approaches to treat immune hot, altered and cold tumours with combination immunotherapies [J].
Galon, Jerome ;
Bruni, Daniela .
NATURE REVIEWS DRUG DISCOVERY, 2019, 18 (03) :197-218
[7]   Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients [J].
Kirilovsky, Amos ;
Marliot, Florence ;
El Sissy, Carine ;
Haicheur, Nacilla ;
Galon, Jerome ;
Pages, Franck .
INTERNATIONAL IMMUNOLOGY, 2016, 28 (08) :373-382
[8]   Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer [J].
Mlecnik, Bernhard ;
Bifulco, Carlo ;
Bindea, Gabriela ;
Marliot, Florence ;
Lugli, Alessandro ;
Lee, J. Jack ;
Zlobec, Inti ;
Rau, Tilman T. ;
Berger, Martin D. ;
Nagtegaal, Iris D. ;
Vink-Borger, Elisa ;
Hartmann, Arndt ;
Geppert, Carol ;
Kolwelter, Julie ;
Merkel, Susanne ;
Gruetzmann, Robert ;
Van den Eynde, Marc ;
Jouret-Mourin, Anne ;
Kartheuser, Alex ;
Leonard, Daniel ;
Remue, Christophe ;
Wang, Julia Y. ;
Bavi, Prashant ;
Roehrl, Michael H. A. ;
Ohashi, Pamela S. ;
Nguyen, Linh T. ;
Han, SeongJun ;
MacGregor, Heather L. ;
Hafezi-Bakhtiari, Sara ;
Wouters, Bradly G. ;
Masucci, Giuseppe V. ;
Andersson, Emilia K. ;
Zavadova, Eva ;
Vocka, Michal ;
Spacek, Jan ;
Petruzelka, Lubos ;
Konopasek, Bohuslav ;
Dundr, Pavel ;
Skalova, Helena ;
Nemejcova, Kristyna ;
Botti, Gerardo ;
Tatangelo, Fabiana ;
Delrio, Paolo ;
Ciliberto, Gennaro ;
Maio, Michele ;
Laghi, Luigi ;
Grizzi, Fabio ;
Fredriksen, Tessa ;
Buttard, Benedicte ;
Lafontaine, Lucie .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (31) :3638-+
[9]   Functional Network Pipeline Reveals Genetic Determinants Associated with in Situ Lymphocyte Proliferation and Survival of Cancer Patients [J].
Mlecnik, Bernhard ;
Bindea, Gabriela ;
Angell, Helen K. ;
Sasso, Maria Stella ;
Obenauf, Anna C. ;
Fredriksen, Tessa ;
Lafontaine, Lucie ;
Bilocq, Amelie M. ;
Kirilovsky, Amos ;
Tosolini, Marie ;
Waldner, Maximilian ;
Berger, Anne ;
Fridman, Wolf Herman ;
Rafii, Arash ;
Valge-Archer, Viia ;
Pages, Franck ;
Speicher, Michael R. ;
Galon, Jerome .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (228)
[10]   Biomolecular Network Reconstruction Identifies T-Cell Homing Factors Associated With Survival in Colorectal Cancer [J].
Mlecnik, Bernhard ;
Tosolini, Marie ;
Charoentong, Pornpimol ;
Kirilovsky, Amos ;
Bindea, Gabriela ;
Berger, Anne ;
Camus, Matthieu ;
Gillard, Melanie ;
Bruneval, Patrick ;
Fridman, Wolf-Herman ;
Pages, Franck ;
Trajanoski, Zlatko ;
Galon, Jerome .
GASTROENTEROLOGY, 2010, 138 (04) :1429-1440