New insight into GARP striking role in cancer progression: application for cancer therapy.
Mohammad Reza LahimchiMajid EslamiBahman YousefiPublished in: Medical oncology (Northwood, London, England) (2022)
T regulatory cells play a crucial role in antitumor immunity suppression. Glycoprotein-A repetitions predominant (GARP), transmembrane cell surface marker, is mostly expressed on Tregs and mediates intracellular organization of transforming growth factor-beta (TGF-β). The physiological role of GARP is immune system homeostasis, while it may cause tumor development by upregulating TGF-β secretion. Despite the vast application of anti- programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte Antigen-4 (CTLA-4) antibodies in immunotherapy, anti-GARP antibodies have the advantage of better response in patients who has resistance to anti-PD-1/PD-L1. Furthermore, simultaneous administration of anti-GARP antibody and anti-PD-1/PD-L1 antibody is much more effective than anti-PD-1/PD-L1 alone. It is worth mentioning that the GARP-mTGF-β complex is more potent than secretory TGF-β to induce T helper 17 cells differentiation in HIV + patients. On the other hand, TGF-β is an effective cytokine in cancer development, and some microRNAs could control its secretion by regulating GARP. In the present review, some information is provided about the undeniable role of GARP in cancer progression and its probable importance as a novel prognostic biomarker. Anti-GARP antibodies are also suggested for cancer immunotherapy.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- papillary thyroid
- induced apoptosis
- cancer therapy
- squamous cell
- cell surface
- cell cycle arrest
- newly diagnosed
- antiretroviral therapy
- hiv infected
- hepatitis c virus
- dendritic cells
- small molecule
- cell proliferation
- hiv positive
- childhood cancer
- lymph node metastasis
- regulatory t cells
- prognostic factors
- peripheral blood
- health information
- patient reported outcomes
- protein protein
- reactive oxygen species