IL4 and skin neoplasm: BTKi impairs macrophage function and reprograms tumor-associated macrophages from a tumoricidal type 1 macrophage (M1) to a tumor-infiltrating M2 phenotype.[21] This shift was associated with CD4 + T cells down-regulating interferon-γ (IFN-γ) and IL-2 and increasing IL-4 and IL-5 levels, cytokines that can promote tumor progression and suppress T helper 1 (Th1)-type responses characterized by IFN-γ production.[22] Orelabrutinib may induce this myeloid environment in the skin, creating a local niche that allows multiple skin tumors to develop and grow in synergy with systemic immune changes.