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The immunosuppressive effect of regulatory T-cells (Treg) is essential for the maintenance of external immune tolerance and is harmful in cancer or chronic infections.
, it is particularly important to study treatment strategies that target Treg cells and their functions in cancer patients.
Although some progress has been made in blocking CTLA-4 or PD-1 inhibitory pathways with monoclonal antibodies (mAb), the primary or obtained resistance of the vast majority of patients to T-cell-mediated anti-tumor immunity makes patients unresponsive to the immunotherapy, and Treg cells appear to be harmful against tumor immunity in most patients and cancer types.
TGF-beta 1, beta 2 and beta 3 can bind to a common subject and play different roles in cancer, which can promote tumor metastasis and inhibit anti-tumor immunity to promote tumor development, on the contrary, it can also inhibit the proliferation of malignant cells and play a role in anti-cancer.
previous studies have shown that suppressing the overall expression level of TGF-beta can cause harmful tumor-promoting effects.
combined blocking garP: TGF-beta 1 and PD-1 have anti-tumor effects The study found that Treg, which expresses anti-GARP:TGF-beta-1 complex antibodies, selectively blocks the production of TGF-beta1 and inhibits the growth of tumors with PD-1 immunotherapy resistance.
And GARP: TGF-beta-1/PD-1 blocker is a non-dependent immuno-mediated response of Fc-R, which increases the function of anti-tumor CD8-T cells without increasing the immersion of immune cells or the removal of Treg cells from tumors.
researchers also found Treg cells that express GARP and demonstrated that one-third of patients with metastasis melanoma were able to produce TGF-beta1.
results show that monoclonal antibodies against GARP:TGF-beta1 can selectively inhibit cancer-promoting TGF-beta protein subtypes, which may be a potential therapeutic drug for patients with PD-1/PD-L1 inhibitor resistance.
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