Clin Exp Med. 2025 Jun 25;25(1):218. doi: 10.1007/s10238-025-01754-4.ABSTRACTAngioimmunoblastic T-cell lymphoma (AITL), a rare subtype of peripheral T-cell lymphoma (PTCL) with regional differences, originates from follicular T helper (Tfh) cells and is characterized by significant immunological involvement. The tumor microenvironment (TME) in AITL is complex, primarily composed of T cells, B cells, plasma cells, follicular dendritic cells and high endothelial venules. Genetically, AITL exhibits the characteristics of TET2 and DNMT3A mutations in hematopoietic stem cells, while RHOA and IDH2 mutations are detected in the Tfh cells. Subsequently, Tfh cells begin to release various chemokines and cytokines to regulate the intricate network of interactions with TME promoting development of AITL. Diagnosis remains challenging for AITL due to diverse clinical presentations and laboratory features resembling changes seen in multiple benign diseases. Several predictive models have been proposed; however, overall prognosis for AITL remains poor. Treatment strategies should be based on the patient's age, physical condition, and comorbidities. Participation in clinical trials is recommended as an initial treatment strategy. Autologous stem-cell transplantation (ASCT) for AITL still remains to be a subject of ongoing debate. Numerous multi-phase clinical trials have been carried out for relapsed/refractory (R/R) AITL. Moreover, CAR-T and CAR-NK therapy represents promising avenues that are worthy of further exploration for the treatment of AITL.PMID:40560424 | DOI:10.1007/s10238-025-01754-4