GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305825/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305825GEOGSEfalseGolcadomide with CD20 T-cell engager extends survival in lymphoma model by boosting T-cell activation and traffickingDespite recent clinical advances in the treatment of diffuse large B-cell lymphoma, relapsed/refractory patients remain an unmet medical need. Immune-based therapies, such as CAR T and T cell bispecific antibodies, redirect T-cells to target antigens expressed on the malignant cells, have demonstrated promising antitumor and clinical activity. However, even with these advanced therapies some patients do not have non-durable responses, potentially due to tumor microenvironment factors such as lack of T-cell infiltration. Golcadomide, a potential first-in-class Aiolos and Ikaros degrading CRBN E3 ligase modulator (CELMoD), has a multifaceted mechanism of action, including direct antitumor effects and T-cell activation. This study demonstrates that through specific degradation of transcription factors, Aiolos and Ikaros, golcadomide enhances T-cell function through increased proliferation and cytokine production. Spatial transcriptomic and multiplex immunofluorescence data revealed that single agent golcadomide treatment enhanced T-cell functions in a syngeneic GEMM lymphoma model, including T-cell activation and trafficking to the TME, suggesting potential synergy with T-cell engagers. In a combination with a CD20xCD3 murine surrogate T-cell engager, golcadomide increased T-cell mediated cytotoxicity against lymphoma cells and extended survival in an aggressive lymphoma GEMM compared to single-agent bispecific treatment. These findings support the clinical rationale for combining these immunotherapeutic modalities to improve outcomes in DLBCL.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 sapiens