By secreting cytokines, NK cells can promote mutual crosstalk of immune cells in the TME, and conversely, the cytokines in the TME can reduce the killing ability of NK cells (65)

By secreting cytokines, NK cells can promote mutual crosstalk of immune cells in the TME, and conversely, the cytokines in the TME can reduce the killing ability of NK cells (65). and Western medicine were analyzed, starting with the effect of macrophages on tumors and their interactions with other cells and then the role of macrophages in conventional treatments was explored. Possible directions of future developments in this field from an all-around multitarget standpoint were also examined. revealed that hemozoin can reduce the quantity of infiltrating TAMs and decrease the expression of MMP9 and MMP2, thus suppressing tumor angiogenesis and slowing down metastasis and tumor growth (27). 3. Conversation between macrophages and the tumor immune microenvironment The TME serves as a place where tumor cells and stromal cells can interact, including fibroblasts, endothelial cells, and both innate- and adaptive-immunity cells (28). The migration of leukocytes into the TME gives rise Panaxtriol to the tumor immune microenvironment (29). Macrophages constitute half of these leukocytes and play a major role in the TME (30). Therefore, focusing on the interactions between macrophages and other cells in the TME offers unique opportunities for malignancy treatment (Fig. 3). Open in a separate window Physique 3 Interactions between TAMs and other cells in the TME. The TME mainly includes stromal cells, fibroblasts and immune cells. The conversation between TAMs and Panaxtriol other components of the TME is usually a unique access point to study the antitumor effect of macrophages. TAMs, tumor-associated macrophages; TME, tumor microenvironment. Interactions between macrophages and cancer-associated fibroblasts (CAFs) CAFs are the most abundant nontumor cells in the TME and perform a prominent function in tumor growth and metastasis. CAFs can simultaneously impact macrophage recruitment and polarization toward the M2 phenotype (31). CAFs are recruited and attach to macrophages under the influence of endostatin in hepatocellular carcinoma (HCC) and secrete GAS6 to promote macrophage M2-type polarization; injection of human antibody IgG78 into tumor-bearing mice specifically attenuated the impact of endostatin around the conversation of CAFs with macrophages, thereby slowing tumor growth (32). When cultured revealed that tumor-derived Tregs in a mouse model could regulate metabolic adaptation of TAMs by inhibiting IFN- production by CD8+ T cells and promoting TAM conversion into the Panaxtriol M2 type (44). In a hypoxic TME, TAMs express triggering receptor expressed on myeloid cell 1 in a manner dependent on hypoxia-inducible factor 1 and upregulate Treg-related chemokine CCL20 to facilitate Treg recruitment to the tumor (45). In that study, there was two-way promotion between the two cell types. TAMs expressing a macrophage receptor enhanced Treg activity in non-small cell lung malignancy (46). Tregs can control polarization and the number of peritoneal macrophages at a specific site of immune-cell aggregation in the abdominal cavity. Similarly, in the peritoneum of patients with epithelial ovarian malignancy, miR-29a-3p and miR-21-5p in exosomes secreted by M2 macrophages increased Treg production by downregulating the STAT3 protein (47). The conversation between the two cell types is not simple linear promotion. In malignant pleural effusion (MPE) of patients with lung malignancy, TAMs produced chemokine CCL22 under the influence of TGF- thus driving Treg recruitment to MPE, and the IL-8 produced by Tregs in MPE could in turn promote TGF- expression in TAMs. In addition, IL-8 was revealed to increase the production of CCL22 and enhanced the immunosuppression in MPE (48). Depletion of Tregs can slow tumor growth in tumor-bearing mice but can also cause an increase in the number of CSF1 receptor (CSF1R)+ TAMs and defeat the purpose of this form of therapy. The inhibition of Tregs and TAMs can also greatly enhance the antitumor action (11). Tregs can interact with TAMs in a variety of ways, and the crosstalk between Tregs and TAMs suggests that the conversation between macrophages and other components of the TME should be considered carefully. To maximize the therapeutic effect, joint targeted steps should be taken Panaxtriol instead Rabbit Polyclonal to ACOT1 of targeting Panaxtriol only macrophages. CD8+ T cells are the first choice for targeted T-cell immunotherapy. They are the main antitumor lymphocytes that can directly recognize and kill tumor cells and play a crucial part in the tumor immune cycle. The concentration of CD8+ T cells infiltrating tumor tissues is usually closely related to the efficacy of antitumor immunity, and depletion of CD8+ T cells can suppress antitumor immunity (42). Studies around the crosstalk between TAMs and CD8+ T cells have mostly been focused on the effect of TAMs on CD8+ T cells through their interactions with Tregs, and there.