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Title: Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition.
Austin Authors: Daly, Roger J;Scott, Andrew M ;Klein, Oliver ;Ernst, Matthias 
Affiliation: Cancer Program, Monash Biomedicine Discovery Institute, Monash University, 23 Innovation Walk, Clayton, VIC, 3800, Australia
Department of Biochemistry & Molecular Biology, Monash University, 23 Innovation Walk, Clayton, VIC, 3800, Australia
Olivia Newton-John Cancer Research Institute
Molecular Imaging and Therapy
Issue Date: 2022
Date: 2022
Publication information: Molecular Cancer 2022; 21(1): 189
Abstract: Over the past decade, immune checkpoint inhibitor (ICI) therapy has been established as the standard of care for many types of cancer, but the strategies employed have continued to evolve. Recently, much clinical focus has been on combining targeted therapies with ICI for the purpose of manipulating the immune setpoint. The latter concept describes the equilibrium between factors that promote and those that suppress anti-cancer immunity. Besides tumor mutational load and other cancer cell-intrinsic determinants, the immune setpoint is also governed by the cells of the tumor microenvironment and how they are coerced by cancer cells to support the survival and growth of the tumor. These regulatory mechanisms provide therapeutic opportunities to intervene and reduce immune suppression via application of small molecule inhibitors and antibody-based therapies against (receptor) tyrosine kinases and thereby improve the response to ICIs. This article reviews how tyrosine kinase signaling in the tumor microenvironment can promote immune suppression and highlights how therapeutic strategies directed against specific tyrosine kinases can be used to lower the immune setpoint and elicit more effective anti-tumor immunity.
DOI: 10.1186/s12943-022-01656-z
Journal: Molecular Cancer
PubMed URL: 36175961
Type: Journal Article
Subjects: CTLA-4
Targeted therapy
Tumor microenvironment
Appears in Collections:Journal articles

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