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Characteristics and developmental trajectory of clinical trials focused on tumor-infiltrating lymphocytes for cancer treatment

Cancer Gene Therapy volume 33, pages 236–247 (2026)Cite this article

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Abstract

Tumor-infiltrating lymphocytes (TIL) have shown promise in cancer immunotherapy, yet their clinical application and developmental trajectory remain insufficiently characterized. In this study, we conducted a cross-sectional, descriptive analysis of interventional clinical trials investigating TIL therapies for cancer treatment registered on ClinicalTrials.gov up to December 31, 2024. Trial characteristics, temporal trends, and treatment strategies were systematically assessed. Among 177 eligible trials, the vast majority were early-phase studies enrolling small patient cohorts. Malignant melanoma was the most frequently studied tumor type. North America conducted the largest number of trials overall, while recent years have seen rapid growth in trial activity and industry sponsorship, particularly in Asia. Cytokine support and immune checkpoint inhibitors (ICIs) were the most common combination strategies. Since 2017, increasing interest has been observed in TIL monotherapy and in TIL–ICI combinations. Genetically engineered TIL trials were less likely to incorporate cytokine support or non-myeloablative chemotherapy, whereas selectively expanded TIL trials more frequently evaluated radiotherapy as a combination strategy. Overall, clinical trials of TIL therapy have primarily focused on early-phase exploration. Cytokines and ICIs remain the predominant combination approaches, while the use of TIL monotherapy has emerged as a growing trend. Continued research efforts and clinical investigation are essential to support the broader and more standardized application of TIL-based therapies in cancer treatment.

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Fig. 1: Flow chart of clinical trial screening.
Fig. 2: Distribution of participants in TIL clinical trials.
Fig. 3: Proportion of TIL clinical trials by tumor type.
Fig. 4: Trends in the number of different TIL types and combination therapy strategies over time.

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Data availability

All data analyzed in this study are publicly available from the ClinicalTrials.gov database (https://clinicaltrials.gov). The datasets generated and/or analyzed during the current study are included in this published article and its supplementary materials.

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Author notes

  1. These authors contributed equally: Jinyi Liu, Chun Xiao, Wei Zhang.

Authors and Affiliations

  1. Department of Phase I Clinical Trial Ward, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China

    Jinyi Liu & Xuebin Wang

  2. Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, China

    Chun Xiao

  3. Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China

    Wei Zhang

  4. Panzhihua University, Panzhihua, China

    Xinhong Li

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Contributions

XW had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis. JL, CX, and WZ contributed equally to this work. Concept and design: JL and WZ. Acquisition, analysis, or interpretation of data: JL, CX, and WZ. Drafting of the manuscript: JL, CX, and WZ. Critical revision of the manuscript for important intellectual content: JL, CX, WZ, and XL. Statistical analysis: JL, CX, and WZ. XW supervised the study and resolved disagreements. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuebin Wang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Clinical trial information

The Ethics Committee of Sichuan Cancer Hospital determined that this study did not involve human subjects; thus, ethical review was waived.

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Supplementary information

Supplementary Table 1. Characteristics in clinical trials of TIL for the treatment of cancer. (download DOCX )

41417_2026_998_MOESM2_ESM.docx (download DOCX )

Supplementary Table 2. Trend changes in characteristics of Autologous Natural TIL & Genetically Engineered TIL & Selectively Expanded TIL trials registered on ClinicalTrials.gov between 1993 to 2016 a

41417_2026_998_MOESM3_ESM.xlsx (download XLSX )

Supplementary Table 3. Summary of individual TIL clinical trials, including study design, tumor type, interventions, combination strategies, and reported outcomes.

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Liu, J., Xiao, C., Zhang, W. et al. Characteristics and developmental trajectory of clinical trials focused on tumor-infiltrating lymphocytes for cancer treatment. Cancer Gene Ther 33, 236–247 (2026). https://doi.org/10.1038/s41417-026-00998-w

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