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RESEARCH PRODUCT

GARP: A Key Target to Evaluate Tumor Immunosuppressive Microenvironment

Carmen GarridoBertrand CollinPierre-simon BellayeEvelyne KohliAlexanne Bouchard

subject

TGF-βTumor microenvironmentimmunosuppressionGeneral Immunology and MicrobiologyQH301-705.5CancerReviewBiologymedicine.diseaseGeneral Biochemistry Genetics and Molecular BiologyBiomarker (cell)Docking (dog)Immune systemGARPCancer researchmedicinecancerbiomarkerBiology (General)General Agricultural and Biological SciencesReceptorFunction (biology)Transforming growth factor

description

Simple Summary Tumors are not only composed of cancer cells but also of various infiltrating cells constituting the tumor microenvironment (TME); all these cells produce growth factors which contribute to tumor progression and invasiveness. Among them, transforming growth factor-β1 (TGF-β1) has been shown to be a potent immunosuppressive cytokine favoring cell proliferation and invasion and to be associated with resistance to anticancer treatments. Glycoprotein-A repetition predominant (GARP) plays a critical role in the activation of TGF-β1 and has been shown to be expressed at the membrane of cancer cells and also of regulatory T cells and platelets in the TME. An increased GARP expression has been shown in a variety of cancers. The objective of this review is to highlight GARP’s expression and function in cancer and to evaluate its potential as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging. Abstract Glycoprotein-A repetitions predominant (GARP) is the docking receptor for latent transforming growth factor (LTGF-β) and promotes its activation. In cancer, increased GARP expression has been found in many types of cancer. GARP is expressed by regulatory T cells and platelets in the tumor microenvironment (TME) and can be also expressed by tumor cells themselves. Thus, GARP can be widely present in tumors in which it plays a major role in the production of active TGF-β, contributing to immune evasion and cancer progression via the GARP-TGF-β pathway. The objective of this review is to highlight GARP expression and function in cancer and to evaluate the potential of membrane GARP as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging. Moreover, as GARP can be secreted, a focus will also be made on soluble GARP as a circulating biomarker.

10.3390/biology10090836https://www.mdpi.com/2079-7737/10/9/836