We therefore question the usefulness of classical immune checkpoint inhibitors for the treatment of relapsed or refractory LCH (or other histiocytic neoplasms), especially given that these LCH-patients often bear the BRAFV600E mutation (44), and that pretherapy intratumoral CD8+ T cell density has been shown to positively correlate with mutational burden, neoantigen load and response to immune checkpoint inhibition in many other neoplastic diseases (103, 104). This evidence concerns the gene CD8A and neoplasm.