Gamma-Delta-T-Cells-in-Cancer-Biology

γ δ T CELLS IN CANCER BIOLOGY Antitumor functions of γδ T 1 Features of human γδ T cell subsets cells have been associated with cytotoxicity and the Subset Paired TCRγ chains Cellular localization Key cytokines produced production of IFNγ, which can Vδ1 Vγ2, Vγ3, Vγ4, Vγ5, Skin, intestine, liver, spleen and act directly on tumor cells to Vγ8 and Vγ9 mucosal tissues • IFNγ and TNF induce the upregulation of Vδ2 • Can produce IL-17 MHC class I expression and Vδ3 Vγ9 Peripheral blood thus enhance CD8+ T cell Vδ5 • IFNγ and TNF responses. By contrast, IL-17 Vγ2, Vγ3 Liver and peripheral blood • Can produce IL-17 production by certain γδ T cell Vγ4 Peripheral blood Not defined subsets recruits immunosup- pressive cells, such as MDSCs Not defined or small peritoneal macro- phages, which can promote 2 Tumor cell recognition by human γδ T cells angiogenesis, tumor cell growth, and inducible TReg CD20-specific antibody cell differentiation. Further- more, γδ T cells producing Leukaemia cell IL-4, IL-10, and/or TGFβ seem to suppress antitumor NKG2D ULBP3 CD20 Fcγ R l l l immune responses by inhibit- ing dendritic cell maturation NKp30 ? B7-H6 ULBP1 NKG2D and/or the effector functions NCRs of γδ T cells and CD4+ and ? MLL5 MICA CD8+ αβ T cells. The TCR γ NKp44 -chain variable regions (Vγ) BTN3A1 Vγ 9 Vδ 2 + TCR that are preferentially associ- NKG2D ated with each functional Phospho- output are also shown. antigen MICA ULBP4 NKG2D Vδ 1+ TCR Unknown BTN3A1 Vγ 9 Vδ 2 + TCR ligand CD155 CD226 Vδ 1+ T cell Interactions mediated HER2 Fcγ R l l l between γδTCRs and NKRs Carcinoma cell HER2-specific Vγ 9 Vδ 2 + T cell antibody and their ligands on the surface of leukemia and carcinoma cells are shown. 3 Antitumor versus protumour roles of γδ T cells Although the cancer cell γδ T cell populations ligands recognized by NCRs in this context have not been formally identified, other Vγ 1 + Vγ 4 + Vγ 1 + Vγ 6 + systems indicate that B7-H6 Vγ 4 + could be the putative ligand Vγ 5 + for NKp30 and MLL5, a ligand IFNγ , IL-17 TNF for NKp44. Tumor specificity IL-4, IL-1β, MDSC IL-10, Direct killing IL-23 for signaling through the Fcγ TGFβ Tumor Immunity TH17 Apoptotic tumor cell cell RIII can be achieved by tumor Small peritoneal antigen-specific monoclonal MHC class I Tumor cell macrophage upregulation antibodies, such as CD20-spe- ↑ CXCL5 · Angiogenesis cific antibody (rituximab) and CTL · CTL suppression TH1 HER2-specific antibody cell NK cell (trastuzumab), used in combi- Direct killing nation with Vγ9Vδ2+ T cell Tumor Growth therapy. TReg cell Creative Biolabs WHAT WE DO: CAR Therapy Services & CAR-T Therapy Development Services Products: Products TCR Modified T Cell Development Services CAR/TCR Vector Systems CAR-NK/Macrophage Development Services CAR/TCR Viral Particles Dendritic Cell Vaccine Development Services CAR/TCR Jurkat Cells γδ T Cells Engineering Services Immune Cell Products © 2022 Creative-Biolabs All Rights Reserved Email: [email protected]