Characteristics and Developmental Trajectory of Clinical Trials Focused on Tumor-Infiltrating Lymphocytes for Cancer Treatment

Background: Tumor-infiltrating lymphocytes (TILs) have shown promise in cancer immunotherapy, but their clinical application and developmental trajectory remain insufficiently characterized. This study aimed to systematically analyze the features and trends of TIL-related clinical trials to inform future trial designs and translational research. Methods: We conducted a cross-sectional analysis of interventional TIL trials for cancer treatment registered on ClinicalTrials.gov up to December 31, 2024. Trial characteristics, temporal trends, and treatment strategies were assessed. Results: Among 177 eligible trials, 98.3% were early-phase studies, and 53.1% enrolled no more than 20 patients. Malignant melanoma was the most frequently studied tumor (32.2%). North America led trial activity (49.2%), with growing industry sponsorship (37.9%). Cytokines (70.1%) and immune checkpoint inhibitors (ICIs; 23.2%) were the most common combination therapies. Since 2017, the proportion of trials using TIL monotherapy significantly increased (P<0.001), alongside a rise in TIL–ICI combinations (P=0.049). Genetically engineered TIL trials showed a lower use of cytokines (vs. autologous, P<0.001; vs. selectively expanded, P=0.007) and non-myeloablative chemotherapy (P=0.003; P=0.020). Selectively expanded TILs were more often combined with radiotherapy (P=0.033; P=0.009). Conclusion: Clinical trials of TIL for tumor treatment have primarily focused on early-phase studies. Cytokines and ICIs remain the predominant combination therapies utilized in TIL clinical trials. The use of TIL monotherapy has emerged as a growing trend. Further research efforts and clinical attention are essential to facilitate the broader application of TIL therapies in clinical practice.