Understanding the interplay between extracellular matrix topology and tumor-immune interactions: Challenges and opportunities.

Modern cancer management comprises a variety of treatment strategies. Immunotherapy, while successful at treating many cancer subtypes, is often hindered by tumor immune evasion and T cell exhaustion as a result of an immunosuppressive tumor microenvironment (TME). In solid malignancies, the extracellular matrix (ECM) embedded within the TME plays a central role in T cell recognition and cancer growth by providing structural support and regulating cell behavior. Relative to healthy tissues, tumor associated ECM signatures include increased fiber density and alignment. These and other differentiating features contributed to variation in clinically observed tumor-specific ECM configurations, collectively referred to as Tumor-Associated Collagen Signatures (TACS) 1-3. TACS is associated with disease progression and immune evasion. This review explores our current understanding of how ECM geometry influences the behaviors of both immune cells and tumor cells, which in turn impacts treatment efficacy and cancer evolutionary progression. We discuss the effects of ECM remodeling on cancer cells and T cell behavior and review recent in silico models of cancer-immune interactions.