Fig. 3

The network of immune cell-derived sEVs. Immune cell-derived sEVs mediate the communication and modulation between immune cells, directly or indirectly determine pro-tumour or anti-tumour effects. a sEVs released by activated CD4 + T cells can activate resting T cells with the assistance of IL-2, promote the proliferation of CD8 + T cells and memory CD8 cytotoxic T cells (CTLs). sEVs released by activated CD8 + T cells can kill cancer cells by cytotoxic molecules and activate bystander CD8 + T cells. However, in a tumor environment, these sEVs promote tumor metastasis. Antigen-specific sEVs released by CD4 + T or CD8 + T cells can inhibit the antigen-presenting ability of DCs or induce their death. sEVs derived from Tregs carry immunosuppressive ligands and miRNAs that inhibit CTL responses, while sEVs derived from MHC-unrestricted γδT cells enhance cytotoxicity of CD8 + T cells and induce apoptosis of tumour cells. b sEVs derived from macrophages (MsEVs) carry membrane pathogen associated molecular patterns (PAPMs) and cytosolic antigens like heat shock protein (HSPs), which can be transferred to DCs. sEVs released by M1 (M1sEVs) or M2 macrophages (M2sEVs) induce the polarisation of macrophages towards the M1 or M2 subtype, respectively. M1sEVs promote T cell proliferation and generation of memory T cells, induce the polarisation of CD4 + T cells towards Th17 subtype. M2sEV suppress anti-tumor effects of CD8 + T and Th17 cells, promote tumor cell invasion by carried miRNAs. c, d SEVs derived from DCs (DCsEVs) and B cells (BsEVs) carry with pMHC complexes, activate CD4 + T cells and promote the cytotoxicity of CD8 + T cells. DCsEVs and BsEVs can induce the polarisation of CD4 + T cells towards Th1 and Th2 subtype, respectively. DCsEVs can also activate the killing effect of NK cells through ligand-receptor binding and directly induce the apoptosis of cancer cells. SEVs mediate antigen transport between DCs and B cells. e SEVs derived from NK cells (NKsEVs) mainly exert cytotoxicity through cytotoxic molecules including granulysin, granzymes, and perforin, as well as induce cell apoptosis through miRNAs and Fas/FasL interaction. f sEVs derived from MDSCs (MDSCsEVs) carry most of the suppressive molecules of MDSCs, inhibit CD8 + T cell activity, induce the polarisation of macrophages towards M2 subtype and promote metastasis of cancer cells