Interleukins in cancer: from biology to therapy

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Abstract

Interleukins and associated cytokines serve as the means of communication for innate and adaptive immune cells as well as non-immune cells and tissues. Thus, interleukins have a critical role in cancer development, progression and control. Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects. This Review aims to unravel some of these complex interactions.

Abstract

This Review provides an update of interleukins in tumour biology, covering the milestones of the latest discoveries of interleukin-related mechanisms in cancer, together with their application in clinical practice. It includes an overview of current clinical trials and breakthrough preclinical concepts.

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Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg (2011)

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

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The Hallmarks of Cancer

Douglas Hanahan, Robert Weinberg (2000)

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New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

Anushka Dongre, Robert Weinberg (2018)

Epithelial-mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell-cell and cell-extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas.

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Author and article information

Contributors

Sebastian Kobold:

ORCID: http://orcid.org/0000-0002-5612-4673

sebastian.kobold@med.uni-muenchen.de

Journal

Journal ID (nlm-ta): Nat Rev Cancer

Journal ID (iso-abbrev): Nat Rev Cancer

Title: Nature Reviews. Cancer

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1474-175X

ISSN (Electronic): 1474-1768

Publication date (Electronic): 3 June 2021

Pages: 1-19

Affiliations

[1 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, , Klinikum der Universität München, LMU, ; Munich, Germany

[2 ]German Center for Translational Cancer Research (DKTK), Munich, Germany

[3 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Einheit für Klinische Pharmakologie (EKLiP), , Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), ; Neuherberg, Germany

[4 ]GRID grid.38142.3c, ISNI 000000041936754X, Division of Cardiovascular Medicine, , Brigham and Women’s Hospital, Harvard Medical School, ; Boston, MA USA

[5 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Medicine, , University of Colorado Denver, ; Aurora, CO USA

Author information

Daria Briukhovetska http://orcid.org/0000-0002-2073-2335

Janina Dörr http://orcid.org/0000-0001-9447-882X

Stefan Endres http://orcid.org/0000-0002-4703-537X

Peter Libby http://orcid.org/0000-0002-1502-502X

Sebastian Kobold http://orcid.org/0000-0002-5612-4673

Article

Publisher ID: 363

DOI: 10.1038/s41568-021-00363-z

PMC ID: 8173513

PubMed ID: 34083781

SO-VID: f812567d-d382-4685-87b3-e035285e3b55

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Interleukins in cancer: from biology to therapy

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Cancer Immunotherapy

Most cited references 246

Hallmarks of Cancer: The Next Generation

The Hallmarks of Cancer

New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

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