Abstract
Cancer immunotherapy is fast rising as a prominent new pillar of cancer treatment, harnessing the immune system to fight against numerous types of cancer. Rho-kinase (ROCK) pathway is involved in diverse cellular activities, and is therefore the target of interest in various diseases at the cellular level including cancer. Indeed, ROCK is well-known for its involvement in the tumor cell and tumor microenvironment, especially in its ability to enhance tumor cell progression, migration, metastasis, and extracellular matrix remodeling. Importantly, ROCK is also considered to be a novel and effective modulator of immune cells, although further studies are needed. In this review article, we describe the various activities of ROCK and its potential to be utilized in cancer treatment, particularly in cancer immunotherapy, by shining a light on its activities in the immune system.
Highlights
We focus on the biological functions of ROCK in various cell types, demonstrating its therapeutic usages as a cancer treatment modality, and suggesting its immunotherapeutic potential to modulate the immunopathology in the tumor microenvironment (TME)
Another study demonstrated that vascular endothelial growth factor (VEGF)/chemokine ligand 18 (CCL18) from IL-4/IL-13 induced M2a type macrophage promoted the invasion of breast cancer cells via the Rho/ROCK signaling pathway, and this could be attenuated by a ROCK inhibitor [78]
ROCK contributes to a variety of cytoskeletal-associated functions in cells by regulating the actin cytoskeleton
Summary
The concept of cancer immunotherapy was first suggested with the plan to harness the patient immune system toward malignant tumor antigens in order to combat cancer. Numerous studies have explored the potential of ROCK-targeted therapy for cancer treatment due to its multiple functions in various cell types in the tumor microenvironment (TME). We focus on the biological functions of ROCK in various cell types, demonstrating its therapeutic usages as a cancer treatment modality, and suggesting its immunotherapeutic potential to modulate the immunopathology in the TME. The Rho/ROCK signaling pathway is generally recognized as an important regulator for cell cytoskeleton and polarity [24]. Along with its ability to regulate the cell cytoskeleton, the Rho/ROCK signaling pathway is involved in cell migration [31]. Under the stimuli of platelet-derived growth factor and lysophosphatidic acid, the Rho/ROCK pathway regulated the cell migration of smooth muscle cells either with or without the involvement of MLC phosphorylation [34]. Both ROCK1 and ROCK2 regulate cell proliferation, and inhibiting them leads to cell cycle arrest and cellular senescence [37]
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