Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.

A prominent activity of the chemokine system is the regulation of immune cells trafficking in tumor microenvironment (TME). This elegant chemotaxis process is regulated by both chemokine receptors (CKRs) stimulation and intracellular factors, such as chemokine, actin cytoskeleton, cell adhesion molecules, membrane fluidity, metabolic reorganization that govern differences in tumor immune cells migration patterns. At the core of tumor immune cell migration and effector functions are three fundamental questions: how CKR signaling triggers morphological changes, how the interplay between actin/selectin and energy metabolism regulates force production, and how cytoskeletal signaling adapts to membrane fluidity. In this review, we discuss the potential influences of CKRs signaling of the actin/selectin cytoskeleton reorganization, membrane fluidity, force regulation, and metabolic reorganization in immune cell chemotaxis. Apparently, the activity of immune cells migration is not regulated solely by chemokine-receptors recognition, as biomechanical-metabolic signaling orchestrate is critical for migratory morphology regulation. By using current knowledge of general chemotaxis mechanisms as a framework, we hope to provide new insights into secondary changes mechanisms of cytoskeleton and morphology network in supporting the tumor immune cells migration. Unraveling the mechanisms underlying chemotaxis and coupled mechanical immune checkpoints holds immense potential for discovering novel therapeutic targets in cancer immunotherapy.