Correspondence on 'H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma' by Immischet al

Endogenous H3.3K27M derived peptide restricted to HLA-A∗02:01 is insufficient for immune-targeting in diffuse midline glioma

“…Recently, the same group responded with a letter presenting modest cytotoxicity data of HSJD DIPG 17 cells being killed by the same TCR-expressing T cells. 15 In contrast, we were unable to detect tetramer binding to any HLA-A∗02:01 + DIPG target cells (including HSJD DIPG 17) containing the K27M mutation, either H3.3 or H3.1, nor any functional recognition, even when pulsed with high concentrations of exogenous K27M peptide ( Figure 3 ). Regarding the K27M peptide presentation, while we acknowledge that the “absence of evidence,” is not the “evidence of absence” in relation to peptide presentation, our sensitive immunopeptidomics and mass spectrometry failed to detect the HLA-A∗02:01 restricted H3.3K27M 26–35 , R M SAPSTGGV neopeptide using DDA methods, as well as sensitive and targeted MRM assays.…”