Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment

Abstract

Within the complex tumor microenvironment, cells experience mechanical cues—such as extracellular matrix stiffening and elevation of solid stress, interstitial fluid pressure, and fluid shear stress—that significantly impact cancer cell behavior and immune responses. Recognizing the significance of these mechanical cues not only sheds light on cancer progression but also holds promise for identifying potential biomarkers that would predict therapeutic outcomes. However, standardizing methods for studying how mechanical cues affect tumor progression is challenging. This challenge stems from the limitations of traditional in vitro cell culture systems, which fail to encompass the critical contextual cues present in vivo. To address this, 3D tumor spheroids have been established as a preferred model, more closely mimicking cancer progression, but they usually lack reproduction of the mechanical microenvironment encountered in actual solid tumors. Here, we review the role of mechanical forces in modulating tumor- and immune-cell responses and discuss how grasping the importance of these mechanical cues could revolutionize in vitro tumor tissue engineering. The creation of more physiologically relevant environments that better replicate in vivo conditions will eventually increase the efficacy of currently available treatments, including immunotherapies.

Status of breast cancer detection in young women and potential of liquid biopsy

“…Increased fibrillar collagen density and radial alignment of collagen are observed in invasive breast tumors and observed in physiologically normal breast involution and in PPBC ( 169 – 171 ). These ECM-based mechanisms inherently improve the motility and invasiveness of breast cancer cells, however, there are also well-documented interactions between ECM dynamics and the immune system, suggesting further downstream effects of the local mechanical involution environment ( 172 , 173 ). Beyond ECM dynamics, there is a distinct role for direct mechanical forces in regulating involution.…”

The application of nanomaterials in tumor therapy based on the regulation of mechanical properties

“…77 Other immune cells are also influenced by mechanical forces and play various roles in tumor immunity. 78 Therefore, the stiffness of the TME plays a critical role in immune escape mechanisms. Modulating the mechanical properties of the TME to enhance immunotherapy represents an effective cancer treatment strategy.…”