Donor T cell (transferred via Donor Lymphocyte Infusion) (DLI T cell)

Donor T cells transferred via donor lymphocyte infusion (DLI) are a form of adoptive cellular therapy used to treat relapsed hematologic malignancies, such as multiple myeloma and leukemia, following allogeneic hematopoietic stem cell transplantation (PMID: 24637911). The therapeutic intent is to harness the graft-versus-leukemia (GvL) effect, where donor-derived immune cells recognize and destroy residual recipient tumor cells. The interaction with lenalidomide and dexamethasone is a clinical strategy designed to pharmacologically augment this immune response. Lenalidomide acts as an immunomodulatory agent by binding to the Cereblon (CRBN) E3 ubiquitin ligase complex, leading to the degradation of Ikaros and Aiolos transcription factors, which in turn stimulates T-cell activation and the production of interleukin-2 (IL-2) and interferon-gamma (PMID: 24233444). Dexamethasone is typically included in these regimens for its direct anti-proliferative effects on malignant plasma cells and its role in managing inflammatory responses. While this combination can significantly enhance the GvL effect and improve clinical outcomes, it also carries a heightened risk of inducing graft-versus-host disease (GvHD) due to the non-specific potentiation of the donor immune system (PMID: 21616951).

Other names

Donor lymphocyteAllogeneic T cellDLI-derived T cellDonor lymphocyte infusion

Lenalidomide enhances the activity of donor T cells by binding to the Cereblon (CRBN) E3 ubiquitin ligase complex, which triggers the proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) (PMID: 24233444). This degradation leads to increased transcription of interleukin-2 (IL-2) and other Th1 cytokines, promoting T-cell proliferation and cytotoxic activity against tumor cells. Dexamethasone acts through the glucocorticoid receptor to induce apoptosis in malignant cells and modulate the immune environment, providing a synergistic anti-tumor effect when combined with DLI and lenalidomide (PMID: 21616951).