Fig. 4

Spatial evolution of the tumor immune microenvironment (TIME) structure during tumor progression. The process of tumor initiation, expansion, and metastases is accompanied by a gamble between the tumor and the TIME, where antitumor immune and immunosuppressive factors coexist and interact with each other. a In the initiation stage, the immune components around the lesion evolve from immune surveillance to immune escape during the evolution of "normal tissue", precancerous lesions, and carcinoma in situ (CIS). b In the expansion phase, the TIME functions in a contact-dependent or distance-dependent manner. c In the metastatic phase, the specific arrangement of immune cells in the metastatic niche establishes a favorable environment for the formation and growth of metastases. PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; Lag-3, lymphocyte-activation gene 3; TLSs, tertiary lymphoid structures; TLR, Toll-like receptor; CXCL12, C-X-C chemokine ligand type 12; CXCR4, C-X-C chemokine receptor type 4; TGF-β, transforming growth factor-β; IL, interleukin; VEGF, vascular endothelial growth factor; ROS, reactive oxygen species; NO, nitric oxide; EGF, endothelial growth factor; Arg1, Arginase-1; CCL5, C–C chemokine ligand type 5; TNF-α, tumor necrosis factor α