GARP: A Key Target to Evaluate Tumor Immunosuppressive Microenvironment

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.