After initiation of tumor, progression and metastasis depend on tightly controlled TME. TME is infiltrated with immune cells including TAMs, TANs, DCs, MDSCs, CD4+ Tcells, CD8+ Tcells, Tregs and CAFs, pro and anti-inflammatory cytokines, and growth factors. New blood vessel networks around the tumor provide nutrients and oxygen for the survival of tumor cells and tumor associated cells. Signaling from stromal cells contribute to the stemness of the cancer cells.