Fig. 4.

TANs’ role in tumor immunology. A specific subset of N1 neutrophils, characterized by the expression of HLA-DR and CD86, can be induced by GM-CSF and IFN-γ [109]. These neutrophils are capable of activating antitumor adaptive immunity by interacting with CD8⁺ T cells and CD4⁺ T cells through MHC-TCR binding [109]. Conversely, the presence of GM-CSF and IL-6 induces another subset of TANs that express CCL4 and CCL3, facilitating the recruitment of macrophages and thereby promoting tumor metastasis [112]. Additionally, TANs exhibiting elevated levels of CD54 and CD11b, along with reduced CD62L expression, have been shown to secrete CXCL10, IL23a, and Arg1. These molecules, in conjunction with IL-12 secreted by macrophages, collaborate to stimulate the secretion of IFN-γ by unconventional αβ T cells, thereby eliciting a type I immune response against tumor cells [116]. Another subset of TANs expressing CD274 (PD-L1), which is differentiated by lactate, can interact with T cells and subsequently hinder their cytotoxicity against tumors [112, 131]. Furthermore, B cells exhibiting high levels of CD45 and B220, as well as low level of CD138, have been reported to be recruited by TANs to plasma cells exhibiting low levels of B220 and CD138, as well as high level of CD45, by contrast [123]. These TANs secrete the cytokine BAFF (BLyS) and the proliferation-inducing ligand APRIL, which not only contribute to B cells recruitment but also the IgM production, along with its switching to IgG or IgA [124]. Noticeably, apart from molecules such as cytokine BAFF (BLyS), APRIL, and IL-21, TNF-α is also reported to increase the movement and support the migration of B cells along with CXCL12 or CXCL13 [123, 132]. Besides, researchers have pointed out the important function of NETs as well as the direct contact of BAFF and BAFF-R in the B cells recruiting process [124]