Blood: PD-1 and MAPK double inhibition "hand in hand" to overcome LCH's T-cell depletion

Langerhans cell tissue cell progenituration (pulmonary Langerhans'cell histiocytosis, LCH) is a relatively rare inflammatory myelin tumor characterized by granuloma, in which a pathogenic CD207-plus dendritic cell (DC) is present in the fissurerogen activated protein kinase (MAPK) pathogenic state.
standard care chemotherapy strategy is not enough for most patients with multisystric diseases, and the best treatment for relapsed and resuscable LCH is not yet clear.
mechanisms for the development of LCH dermitis, the role of inflammation in the pathogenesis of LCH, and the potential effects of immunotherapy are not clear.
T lymphocytes are the main immune cells in LCH skin loss Sengal et al. through the analysis of Immune cells soaked in LCH skin loss found that the most prominent immune cells in LCH skin loss is T lymphocytes.
T lymphocytes in the LCH micro-environment showed "fatigue" esogram CD8 plus and CD4 plus T cells both showed "fatigue" espressoes with high expression of immune checkpoint subjects.
the LCH tree protrusion cell high expression checkpoint receptor.
expression of Tc1/Tc2 cytokine in CD8-T cells in dermration decreased and the function of the effector was impaired.
, regulatory T-cells (Tregs) in the dermical damage still have normal inhibitory activity.
MEK inhibitors or PD-1 antibody therapy can reduce the burden of disease in LCH mice with anti-PD-1 or MAPK inhibitors to treat BRAFV600ECD11c LCH mice can reduce the area of lesions;
, it is worth noting that MAPK inhibitors and anti-PD-1 combined therapy can significantly reduce THED8-T cells and myelin-like LCH cells in LCH dermal loss in a collaborative manner.
above, the above results are consistent with those of another LCH model (MAPK over-activation of myelin LCH cells, which drives the depletion of functionally depleted T-cells in the LCH microenvironment).
the study highlights the potential therapeutic strategy of mapK and checkpoint joint inhibition for LCH.