For instance, collagen fibers can bind to leukocyte associated immunoglobulin‐like receptor‐1 (LAIR‐1) and reduce NK and T cell activation (Figure 7A‐3).[100] LAIR‐1 signaling has been shown to lead to T cell exhaustion, rendering lung tumors resistant to programmed cell death protein 1 (PD1)/PD‐L1 therapy.[101] Likewise, the fibrotic ECM, physically confining the tumor mass, functions as a physical barrier that affects the infiltration of cytotoxic T cells and the delivery of chemotherapeutics (Figure 7A‐4). The gene discussed is CD274; the disease is neoplasm.