A high proportion of LAG-3<sup>+</sup> T cells was found in only a few cases with AML; however, a significantly higher proportion of coexpression of CTLA-4 and LAG-3 in the CD3<sup>+</sup> and CD8<sup>+</sup> T-cell subsets was detected.
CTLA-4 inhibitor ipilimumab exhibits specific potency in treating relapsed AML patients with extramedullary disease in later post-transplantation stage.
CTLA-4 expression was moderately higher on αβ<sup>+</sup> and γδ<sup>+</sup> T-cells in ALL (p=0.077 and 0.077, respectively), whereas HLA-ABC expression was significantly higher in AML blast cells (p=0.0182).
CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease.
Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g.AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients' T cells against leukemic cells.
Novel monoclonal antibodies that recruit and promote proximity-induced cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as anti CD33/CD3, e.g., AMG 330) or block immune checkpoint pathways such as CTLA4 (e.g., ipilimumab) or PD1/PD-L1 (e.g., nivolumab) unleashing the patients T cells to fight leukemic cells are being evaluated in clinical trials in patients with AML.
We studied the expression of programmed death ligand 1 (PD-L1), PD-L2, programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) mRNA in CD34+ cells from myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) patients (N=124).
Thus, this study provides the first evidence that killing of leukaemic cells from AML patients may be obtained by the engagement of CTLA-4 with its ligands, opening the way to a novel potential therapeutic approach based on triggering the CTLA-4 molecule to circumvent chemoresistance in AML.