Faculty, Staff and Student Publications

Publication Date

5-2-2022

Journal

Clinical Cancer Research

Abstract

Purpose: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL) historically yields a 40%-50% response rate in metastatic melanoma. However, the determinants of outcome are largely unknown.

Experimental design: We investigated tumor-based genomic correlates of overall survival (OS), progression-free survival (PFS), and response to therapy by interrogating tumor samples initially collected to generate TIL infusion products.

Results: Whole-exome sequencing (WES) data from 64 samples indicated a positive correlation between neoantigen load and OS, but not PFS or response to therapy. RNA sequencing analysis of 34 samples showed that expression of PDE1C, RTKN2, and NGFR was enriched in responders who had improved PFS and OS. In contrast, the expression of ELFN1 was enriched in patients with unfavorable response, poor PFS and OS, whereas enhanced methylation of ELFN1 was observed in patients with favorable outcomes. Expression of ELFN1, NGFR, and PDE1C was mainly found in cancer-associated fibroblasts and endothelial cells in tumor tissues across different cancer types in publicly available single-cell RNA sequencing datasets, suggesting a role for elements of the tumor microenvironment in defining the outcome of TIL therapy.

Conclusions: Our findings suggest that transcriptional features of melanomas correlate with outcomes after TIL therapy and may provide candidates to guide patient selection.

Keywords

Cell- and Tissue-Based Therapy, Endothelial Cells, Genomics, Humans, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating, Melanoma, Neoplasms, Second Primary, Tumor Microenvironment

DOI

10.1158/1078-0432.CCR-21-1060

PMID

35190823

PMCID

PMC9064946

PubMedCentral® Posted Date

11-2-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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