Fig. 3

Signaling pathways, microenvironment, and targeted treatments in Langerhans cell histiocytosis. A The precursor cells of LCH cells. (a) Early myeloid progenitor cells are the precursor cells of LCH cells, regardless of the risk of disease. MAPK pathway activation promotes the proliferation and differentiation of precursor cells. (b) The direct precursor cells of LCH cells in peripheral blood are still controversial. B MAPK pathway mutations and treatments targeting specific mutations. C LCH cells seeded the tumor microenvironment. (a) The interaction between LCH cells and Tregs via ICOS-ICOS ligand promotes the accumulation of Tregs in the microenvironment, which promotes an immunosuppressive microenvironment. (b) The interaction between LCH cells and CD8⁺ T cells via PD-1 and PD-L1 suppresses CD8⁺ T cell function and helps LCH cells escape immunosurveillance. PD-1 inhibitors act in synergy with MAPK inhibitors. (c) CCL5 produced by LCH cells promotes the accumulation of eosinophils in lesions via chemotaxis. D Survival and accumulation of LCH cells induce the formation of lesions. (a) The activation of the MAPK pathway in LCH cells upregulates BCL-XL expression in LCH cells and promotes the survival of those cells. (b) The activation of the MAPK pathway in LCH cells downregulates CCR7 expression on the cell membrane via negative feedback, inhibits the migration of LCH cells to draining lymph nodes, and promotes LCH cell accumulation in lesions