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In this context, the use of blocking antibodies, drug antagonists, dominant-negative receptors (DNR), and knocking out mechanisms such as CRISPR/Cas9 and shRNA to suppress the inhibitory checkpoints like PD-1/PDL-1 as well as administrating the costimulatory molecules like CD28 and 4-1BB, in combination with CAR-T cell would be promised in cancer treatment

Key mechanisms include: Stimulation of collagen and elastin synthesis in fibroblasts Activation of lysyl oxidase for collagen cross-linking Enhanced production of glycosaminoglycans and decorin Modulation of metalloproteinase activity for controlled matrix breakdown The copper ion serves as an essential cofactor for enzymes involved in collagen synthesis and provides antioxidant protection through superoxide dismutase activation

Mullin S, Smith L, Lee K, DSouza G, Woodgate P, Elflein J, et al

Zheng Y, Verhoeff TA, Perez Pardo P, Garssen J, Kraneveld AD