The Potential Role of Tumor Microorganisms in Remodeling Tumor Biomechanical Signals and Application Strategies in Tumor Therapy

The tumor microenvironment (TME) is a highly dynamic and heterogeneous system composed of tumor cells, stromal cells and non-cellular components that collectively govern tumor initiation, progression, and metastasis. Beyond host-derived components, accumulating evidence has established that microorganisms are integral constituents of the TME. These tumor-associated microbes not only affect tumor cells directly but also reshape the TME. Importantly, microbial-driven remodeling of the TME is accompanied by changes in its biomechanical properties. These alterations introduce a biophysical dimension of the TME that operates alongside biochemical signaling. Studies have shown that certain microorganisms reshape mechanotransduction pathways within tumor cells. Such biomechanical alterations enhance tumor cell adaptability to shear stress, promote survival in circulation, and facilitate invasion and colonization at distant sites. Although direct evidence linking microbes to specific biomechanical changes in tumors remains limited, these preliminary insights point to a largely unexplored yet highly promising frontier. This review explores the physical properties of the TME and delineates the association between microorganisms and the dynamics of these physical signals. It then examines strategies for leveraging microorganisms in tumor therapy. Understanding these interactions may reveal novel therapeutic targets to harness microbial influences and inhibit tumor progression.