Fig. 1

Crosstalk in the TIME during tumor development. The processes of tumor initiation, expansion, and metastasis are governed by the TIME, where immunosuppressive and antitumor immune crosstalk play an important role. During the tumor initiation stage, cancer cells escape from immune surveillance. While tumor expansion, contact-dependent or independent crosstalk between tumor and TIME affects the production of various cytokines that help in the polarization of antitumor immune response in the immunosuppressive TIME. During metastasis, tumor-derived exosomes help in the requirement and arrangement of immunosuppressive immune cells for favorable premetastatic niche formation and growth of metastases. TGF-β, transforming growth factor-β; GM-CSF, granulocyte–macrophage colony-stimulating factor; CCL28, C–C chemokine ligand type 28; IL, interleukin; TNF-α, tumor necrosis factor α