However, the Th2 response triggered by cancer promotes the growth of cancer cells [34]. of cells and two types of cytokines for cancer immunotherapy as well as combination immunotherapy. This landscape framework provides a quantitative way to understand the underlying mechanisms of the interplay between cancer and the immune system for cancer tumorigenesis and development. and tumour necrosis factor (TNF)-with a 3PO total of 26 nodes. The interactions among the nodes are listed in the electronic supplementary material, table?S1. We chose representative immune IL12RB2 cells and their associated cytokines closely related to cancer cells for the immune response from the existing literature. We also selected the regulations among these cancer cells, immune cells and cytokines from the literature search. Dendritic cells (mDCs) are antigen-presenting cells of the immune system. They trigger the adaptive responses when detecting antigens from cancer cells. Immature dendritic cells (iDCs) have been considered suppressive and tolerogenic to cancer immunity [32]. NK cells and CD8+ are the main effective 3PO killer cells for the innate immune response and the adaptive immune response, respectively. T helper cells are central to the development of an immune response by activating antigen-specific effector cells and recruiting cells of the innate immune system. Th1 cells activate antigen-presenting cells (APCs) and induce the production of the type of antibodies that can enhance the chances of cancer cells turning into APCs. However, the Th2 response triggered by cancer promotes the growth of cancer cells [34]. Th17 cells play a potent proinflammatory role in cancer microenvironments [25]. M1 plays a classic role in the Th1 response and in mediating resistance against cancer cells. M2 takes part in the inflammatory process [23]. In addition, TAN plays an important role in tumour growth and progression 3PO [23]. It is evident that immune responses in cancer are negatively regulated by immunosuppressive cells (Treg) and MDSCs [28]. Cytokines are produced by the cells and regulate other cells through activation or repression. Cytokines can thus mediate the cellCcell interactions. The different cytokines are chosen according to different cell types for the network building. The whole network is shown in figure 1. Open in a separate window Figure 1. The cancerCimmune system. The network includes 26 nodes and 107 interaction links. Cerulean ellipses represent cells and yellow diamonds represent cytokines. Black solid arrows and bars represent cellCcell activation and inhibition, respectively. Red dashed arrows and bars represent cytokineCcell activation and inhibition, respectively. Green dashed arrows represent cellCcytokine production. For the major cellCcell interactions, Th1 inhibits cancer cells by activating the APCs, while Th2 activates cancer cells by promoting their proliferation. M1 activates Th1 and inhibits cancer cells. M2 activates cancer cells through an inflammatory process [23]. CD8+, Th1 and Th2 are activated by mDCs. Accumulation of iDCs inhibits mDC proliferation and activates Treg through stimulating its proliferation [26]. TAN activates CD8+ by enhancing proliferation [33]. The cancer cells and 3PO MDSCs form a positive feedback loop through PGE2 and COX-2. MDSCs activate Treg by inducing its expansion through the ARG1 pathway. MDSCs inhibit the CD8+ response [28]. 3PO NK cells and CD8+ inhibit cancer cells as effective killers. The cancer->cancer interaction does not just refer to the cancer growth by itself. It can be activated by the self-production of cytokines, such as IL-1 [34], which is not included in the cancerCimmune network in order to.