This Letter examines evidence that ganoderic acid DM (GA-DM) is associated with caspase activation, changes in autophagy markers, and increased human leukocyte antigen (HLA) class II-restricted interleukin-2 (IL-2) release in a peptide-specific T-cell hybridoma assay using engineered diffuse large B-cell lymphoma (DLBCL) models, and outlines the viability-controlled tissue and ex vivo studies needed to assess autophagic flux and clinical relevance.