LAUSR

21 days. Tumor growth was measured using callipers. Results: PIM1/2/3 were ubiquitously expressed in primary and cultured RS cells but not in healthy donor‐derived peripherial B cells. PIM1/2/3 expression was driven by JAK‐STAT and NFκB activity. Genetic or chemical PIM inhibition with a newly developed pan‐PIM inhibitor, sel24, induced RS cell apoptosis. PIM inhibition decreased cap‐dependent protein translation, blocked JAK‐STAT signaling, and markedly attenuated NFκB‐dependent gene expression. In a cHL xenograft model, sel24 delayed tumor growth by 95.8% (p = 0.0002). Furthermore, sel24 decreased the expression of multiple molecules engaged in developing the immunosuppressive microenvironment, including galectin‐1 and PD‐L1/2. In co‐culture experiments, Jurkat T‐cells incubated with sel24‐treated RS cells exhibited higher expression of CD25 and CD69 activation markers than T‐cells co‐incubated with control RS cells. Conclusions: Taken together, our data indicate that PIM kinases in cHL exhibit pleiotropic effects, orchestrating tumor immune escape and supporting RS cell survival. Inhibition of PIM kinases decreases RS cell viability and disrupts signaling circuits that link these cells with their niches. Thus, PIM kinases are promising therapeutic targets in cHL.