A pooled analysis of efficacy outcomes of TIL in advanced MEL patients treated at Moffitt Cancer Center
College
College of Arts and Sciences
Mentor Information
Dr. Lilit Karapetyan
Description
Tumor-infiltrating lymphocyte (TIL) therapy induces durable responses in a subset of patients with metastatic melanoma, yet determinants of efficacy remain incompletely defined. We performed integrated immunophenotypic and spatial transcriptomic profiling of TIL infusion products and matched tumor microenvironments (TMEs) from patients treated in early-phase TIL-based trials at Moffitt Cancer Center. The objective response rate was 36%, with a median progression-free survival (PFS) of 10 months. Responders exhibited infusion products enriched for CD8⁺ T cells, stem-like memory (TSCM) CD8⁺ subsets, and LAG3⁺CD8⁺ T cells, along with enhanced TIL persistence in the periphery. Notably, prior exposure to immune checkpoint was associated with a significant reduction in CD8⁺ TSCM frequency and diminished co-stimulatory receptor expression, suggesting a negative imprint of pre-treatment on TIL quality. Within the harvested tumors, the presence of tertiary lymphoid structures (TLS) strongly correlated with response and improved PFS, independent of tissue origin or viable tumor content. Spatial transcriptomic profiling revealed an immune signature characterized by augmented antigen presentation, interferon signaling, and B cell activation in responders. Collectively, these findings define an integrated immunologic framework linking TIL infusion product features and the TME to favorable clinical outcomes.
A pooled analysis of efficacy outcomes of TIL in advanced MEL patients treated at Moffitt Cancer Center
Tumor-infiltrating lymphocyte (TIL) therapy induces durable responses in a subset of patients with metastatic melanoma, yet determinants of efficacy remain incompletely defined. We performed integrated immunophenotypic and spatial transcriptomic profiling of TIL infusion products and matched tumor microenvironments (TMEs) from patients treated in early-phase TIL-based trials at Moffitt Cancer Center. The objective response rate was 36%, with a median progression-free survival (PFS) of 10 months. Responders exhibited infusion products enriched for CD8⁺ T cells, stem-like memory (TSCM) CD8⁺ subsets, and LAG3⁺CD8⁺ T cells, along with enhanced TIL persistence in the periphery. Notably, prior exposure to immune checkpoint was associated with a significant reduction in CD8⁺ TSCM frequency and diminished co-stimulatory receptor expression, suggesting a negative imprint of pre-treatment on TIL quality. Within the harvested tumors, the presence of tertiary lymphoid structures (TLS) strongly correlated with response and improved PFS, independent of tissue origin or viable tumor content. Spatial transcriptomic profiling revealed an immune signature characterized by augmented antigen presentation, interferon signaling, and B cell activation in responders. Collectively, these findings define an integrated immunologic framework linking TIL infusion product features and the TME to favorable clinical outcomes.
