Tumor-Infiltrating Lymphocyte (TIL) Therapy for Metastatic Melanoma

Source: Physicians Weekly, June 2022

For a study, researchers sought to interrogate tumor samples initially collected to generate TIL infusion products that yielded tumor-based genomic correlates of overall survival (OS), progression-free survival (PFS), and response to therapy. Data from 64 samples using whole-exome sequencing (WES) revealed a positive relationship between neoantigen load and OS, but not PFS or response to therapy. RNA sequencing of 34 samples revealed that PDE1C, RTKN2, and NGFR expression was elevated in responders with improved PFS and OS. ELFN1 expression was enriched in patients with an unfavorable response, poor PFS, and OS, whereas ELFN1 methylation was increased in patients with favorable outcomes. In publicly available single-cell RNA sequencing datasets, expression of ELFN1, NGFR, and PDE1C was found primarily in cancer-associated fibroblasts and endothelial cells in tumor tissues across different cancer types, implying a role for tumor microenvironment elements in determining the outcome of TIL therapy. Investigators’ findings suggested that transcriptional features of melanomas correlate with outcomes after TIL therapy and may help guide patient selection.

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