Clinical factors associated with growth and neoantigen reactivity of tumor infiltrating lymphocytes from metastatic epithelial cancers

PMCID: PMC12179044

PMID: 40536705

DOI: 10.1007/s00262-025-04091-3

Journal: Cancer immunology, immunotherapy : CII

Publication Date: 2025-6-19

Authors: Gustafson AM, Dinerman AJ, Hitscherich KJ, Parkhurst MR, Halas H, et al.

Key Points

• Lung metastases demonstrated superior TIL growth (95%) compared to other resection sites
• 51% of TIL harvests showed high neoantigen reactivity, with significant variation by cancer type
• Prior immune checkpoint blockade reduces the likelihood of generating highly reactive TIL

Summary

This prospective study investigated tumor-infiltrating lymphocyte (TIL) growth and neoantigen reactivity across various epithelial cancers, expanding on previous research primarily focused on melanoma. Researchers analyzed 291 metastatic tumor resections, examining TIL characteristics and potential for adoptive cell therapy across different cancer types and patient characteristics.

The study revealed significant variability in TIL growth and reactivity based on tumor origin and prior treatments. Notably, lung metastases demonstrated the highest TIL growth (95%) and reactivity, while hepatic resections showed the lowest growth rates (69%). Of the 263 TIL harvests processed, 51% exhibited high neoantigen reactivity, 26% showed weak reactivity, and 23% demonstrated no reactivity. Critically, patients previously exposed to immune checkpoint blockade were less likely to have highly reactive TIL (p = 0.0325).

These findings provide important insights for clinicians considering TIL therapy, suggesting that tumor origin, prior immunotherapies, and metastatic site significantly impact TIL potential. The research contributes to more strategic planning of TIL harvests and sequencing of immunotherapeutic approaches in epithelial cancers.