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Background Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) is an FDA-approved treatment for metastatic melanoma and continues to be studied in other cancers. 1–5 As a common site of metastatic disease, the liver is potentially a useful site for TIL procurement, but only if the procedures can be performed with an acceptably low risk of significant complications. This study reviewed a single institution experience with hepatic TIL procurement to evaluate safety, share institutional practices, and discuss technical considerations.Methods This was a retrospective analysis of 158 patients who underwent liver resection for TIL between 2000 and 2024 at a single institution. The primary indication for surgery was TIL procurement, excluding those patients with clinical indications for metastasectomy. The cohort was divided into those with metastatic melanoma or metastatic epithelial cancers. The primary study outcomes were 30-day morbidity, 30-day mortality and 90-day mortality.Results Among 158 patients who had liver resection for TIL, 81 (51%) had melanoma and 77 (49%) had epithelial cancer. Patients received a median of 2 [IQR, 1-3] prior lines of prior systemic therapy, and 44% of patients with epithelial cancer had prior oxaliplatin or irinotecan exposure. Minimally invasive resection was performed in 35% (n = 28) of melanoma and 55% (n = 42) of epithelial cancer cases. Liver segment III was the most common (50%) anatomic site of resection ( figure 1), and 73% of operations were non-anatomic wedge resections. Median time to discharge clearance was 5 days and 3 days for the melanoma and epithelial cohorts respectively. Clavien-Dindo grade III+ complication rates were 5% (n = 4) and 7% (n = 5) respectively, with biloma being the most common. For the entire study population, the 30-day and 90-day mortality rates were 1% (n = 2) and 10% (n = 16), none of which were attributed to surgery.Conclusions In highly selected patients, liver resection for TIL procurement can be performed safely with a low complication rate. Nonetheless, especially as compared with other anatomic sites, patient selection for liver procurement can be more complex and the surgery itself carries potential risks. Patients should be discussed in a multidisciplinary setting with both medical and surgical expertise reaching a consensus on the optimal site to ensure these procedures are performed optimally and safely in patients who have significant competing risks due to metastatic cancer.References Seitter SJ, et al. Impact of prior treatment on the efficacy of adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma. Clin Cancer Res 2021;27(19):5289-5298.Lowery FJ, et al. Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial. Nature Medicine 2025;31(6):1994-2003.Zacharakis N, et al. Breast cancers are immunogenic: immunologic analyses and a phase II pilot clinical trial using mutation-reactive autologous lymphocytes. J Clin Oncol 2022;40(16):1741-1754.Lou E, et al. Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial. Lancet Oncol 2025;26(5):559-570.Creelan BC, et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med 2021;27(8):1410-1418.Ethics Approval This protocol (03-C-0277) was performed at the Surgery Branch, National Cancer Institute, and obtained ethics approval in compliance with the IRB in accordance with International Council on Harmonization Good Clinical Practice and relevant portions of the USA Code of Federal Regulations. Informed written consent was provided by all participants, and the trial was reviewed annually by the Center for Cancer Research Safety Monitoring Board.Abstract 370 Figure 1Involvement of Liver Segments in Metastasectomy to Obtain Tumor-Infiltrating Lymphocytes. Heat map of a liver demonstrating involvement of each segment in liver TIL harvest for ACT in 158 patients with metastatic melanoma and epithelial cancers