JAK/STAT Pathway in Classical Hodgkin Lymphoma: From Pathogenic Mechanisms to Therapies

The JAK/STAT pathway is the primary mechanism for cytokine signaling and plays a pivotal role in classical Hodgkin lymphoma (cHL). The JAK/STAT pathway’s abnormal activation contributes to the development and maintenance of tumors. Both intracellular aberrant gene mutations and extracellular cytokine stimulation can continuously activate JAK/STAT pathway, promoting the proliferation, survival and immune evasion of Hodgkin Reed-Sternberg (HRS) cells, the tumor cells of cHL. Moreover, JAK/STAT pathway mediates the formation of an inhibitory tumor micro-environment (TME), as it can regulates the recruitment, differentiation, proliferation and function of various immune cells in the tumor micro-environment (TME) of cHL, including immune effector cells such as CD4+ Th cells, CD8+ T cells, NK cells and immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs), with cytokines binding to corresponding receptors on the surfaces of these cells. Blocking the JAK/STAT pathway can impede the growth of HRS cells and modulate the overall activity of immune cells within the TME of cHL, suggesting that JAK/STAT inhibition might be a viable treatment option for cHL.This review will summarize the performance of JAK/STAT pathway in the pathogenesis of cHL, its effect on immune cells in TME, and the performance of JAK/STAT inhibition in clinical trials, while highlighting potential future directions for JAK/STAT inhibition in cHL treatment.