[Tumor-infiltrating lymphocyte preparations have been in the fight against cancer for 40 years].

This review article summarizes the development of tumor-infiltrating lymphocyte (TIL) based immunotherapy, from the pioneering work of Rosenberg, Spiess and Lafreniere to the 2024 regulatory approval of lifileucel, the first cell therapy authorized for the treatment of solid tumors. A key advantage of TIL therapy over the chimeric antigen receptor (CAR) T-cell technology is its polyclonal T-cell receptor repertoire, which enables more effective recognition of heterogeneous tumor cell populations. The therapeutic approach is based on the ex vivo expansion and activation of lymphocytes isolated from a patient's own tumor, followed by their reinfusion after lymphodepleting conditioning. The review details the major technological advances in the field, with particular emphasis on the significance of "young TIL" protocols, which preserve proliferative capacity and prevent terminal differentiation by shortening culture duration. Current challenges are also discussed, including the need for more precise selection of tumor-reactive T cells, improved tumor homing and infiltration, and reduction of treatment-associated systemic toxicities. Next-generation strategies, including modified cytokines and genetically engineered TILs, aim to replace high-dose IL-2 and intensive chemotherapy, thereby reducing side effects. Overall, the approval of lifileucel validates the clinical relevance of TIL therapy. Fine-tuning the technology through standardized manufacturing and modulation of the tumor microenvironment promises to expand its application to other solid malignancies, fundamentally reshaping cancer treatment. By addressing the limitations of earlier methods, modern TIL therapy serves not as a final solution, but as a transitional foundation for more precise and controllable cellular immunotherapies. Orv Hetil. 2026; 167(19): 740-745.