JS007 could effectively bind to CTLA-4 and induce an immune response in vitro. Potent in vivo antitumor activity of JS007 was observed. Increased T cell infiltration and T regulatory (Treg) cell depletion in tumor mic...
Tregs were observed to regulate CD4+, but not CD8+, T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. These data have important implications for T cell immunotherapy in...
Recent studies have shown that T cells from patients with cutaneous T-cell lymphoma can be induced into cells with a Treg phenotype (Berger et al., 2005). To determine whether regulation of CTLA-4 is abnormal in malignant T cells, we studied CTLA-4 regulation in a disease of memory T ...
Video S2. An instance of polyclonal Treg cell activation within the TME, related to Figure 1 Video S3. Activation of tumor-associated Treg cells depends on cDCs, related to Figure 2 Video S4. Dynamics of HA-Treg and HA-Th cell activation, related to Figure 3 Video S5. CTLA-4 blockade ...
The biological function of CTLA-4 The biological activity of CTLA-4 and its expression is crucial for controlling T cell activation. Serine/threonine phosphatase family members, including PP2A and PP6, interact with CTLA-4 to block CD28 signaling downstream pathways [48]. Treg cell-intrinsic signa...
In Ctla4h/m mice expressing both human and mouse CTLA4 genes, anti-CTLA-4 antibodies that bind to human but not mouse CTLA-4 efficiently induce Treg depletion and Fc receptor-dependent tumor rejection. The blocking antibody L3D10 is comparable to the non-blocking Ipilimumab in causing tumor ...
CTLA-4 blockade depends on several factors including Treg cells, T-cell infiltration, CD8 + T-cell activation, and tumor-associated macrophage (TAMs) recruitment (Fig.1). Treg cells are a subpopulation of immune cells required for self-tolerance and to prevent autoimmune diseases [102]. Th...
Considering the different affinity of CD86 and CD80 for CD28 and CTLA-4, respectively, and the constitutive expression of CTLA-4 in Treg cells, cancer cells could induce antigen tolerance towards themselves by modulating Treg cell functions [57]. Such hypotheses appear to be in agreement with ...
CTLA-4 antibodies have also been used to induce antibody-dependent cell-mediated cytotoxicity (ADCC) of Tregs specific to the tumor microenvironment, thus reducing immune tolerance to the tumor. CTLA-4 antibodies have been therefore used with varying success to treat some types of cancer. Thus, ...
[23]Ghosh T, Nandi P, Ganguly N, Guha I, Bhuniya A, Ghosh S, et al. NLGP counterbalances the immunosuppressive effect of tumor-associated mesenchymal stem cells to restore effector T cell functions. Stem Cell Res Ther. 2019;10(1):296.10.1186/s13287-019-1349-zSearch in Google ScholarPu...