利用目前可用的技术，不太可能在肿瘤中直接观察肿瘤-免疫相互作用，但基于临床数据的计算模拟可以为检验假设提供见解。据推测，胶原蛋白的模式是作为免疫逃逸机制而进化的，但人们对免疫-胶原蛋白相互作用的确切性质知之甚少。量化鳞状细胞癌中胶原纤维排列的空间数据表明晚期疾病与高度排列的纤维相关。我们的计算模型框架区分两种假设：免疫细胞迁移（1）平行于或（2）垂直于胶原纤维方向移动。该模型概括了免疫与细胞外基质的相互作用，其中胶原蛋白模式提供免疫保护，导致疾病阶段和免疫覆盖范围之间出现新的反比关系。在这里，计算模型通过定义核心细胞间相互作用函数提供了重要的机制见解，该函数考虑了局部（细胞尺度）到全局（肿瘤尺度）空间相互作用的范围。短程相互作用内核提供了肿瘤细胞在具有强 Allee 效应的条件下生存的机制，而不对称的肿瘤-免疫相互作用内核导致较差的免疫反应。因此，肿瘤-免疫相互作用核的长度尺度驱动肿瘤生长和浸润。© 2024。作者。

Direct observation of tumor-immune interactions is unlikely in tumors with currently available technology, but computational simulations based on clinical data can provide insight to test hypotheses. It is hypothesized that patterns of collagen evolve as a mechanism of immune escape, but the exact nature of immune-collagen interactions is poorly understood. Spatial data quantifying collagen fiber alignment in squamous cell carcinomas indicates that late-stage disease is associated with highly aligned fibers. Our computational modeling framework discriminates between two hypotheses: immune cell migration that moves (1) parallel or (2) perpendicular to collagen fiber orientation. The modeling recapitulates immune-extracellular matrix interactions where collagen patterns provide immune protection, leading to an emergent inverse relationship between disease stage and immune coverage. Here, computational modeling provides important mechanistic insights by defining a kernel cell-cell interaction function that considers a spectrum of local (cell-scale) to global (tumor-scale) spatial interactions. Short-range interaction kernels provide a mechanism for tumor cell survival under conditions with strong Allee effects, while asymmetric tumor-immune interaction kernels lead to poor immune response. Thus, the length scale of tumor-immune interaction kernels drives tumor growth and infiltration.© 2024. The Author(s).