Tumor-Reactive cd8+ tcells in metastatic gastrointestinal cancer refractory to chemotherapy

Simon Turcotte, Alena Gros, Eric Tran, Chyi Chia R. Lee, John R. Wunderlich, Paul F. Robbins, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate whether patients with metastatic gastrointestinal adenocarcinomas refractory to chemotherapy harbor tumor-reactive cytotoxic T cells. Experimental Design: Expansion ofCD8 + tumor-infiltrating lymphocytes (TIL) and cancer cell lines was attempted from gastrointestinal cancer metastases in 16 consecutive patients for the study of antitumor immune recognition. Retroviral transduction of genes encoding T-cell receptors (TCR) was used to define HLA-restriction elements and specific reactivity. Results: TIL were expanded from metastases in all patients, and new tumor cell lines were generated in 5 patients. Autologous tumor recognition without cross-reactivity against allogeneic HLA-matched gastrointestinal tumors was found in CD8 + TIL from 3 of these 5 patients. In a patient with gastric cancer liver metastases, the repertoire of CD8 + TIL was dominated by cytolytic sister clones reactive to 2 out of 4 autologous cancer cell lines restricted by HLA-C*0701. From the same patient, a rare CD8 + TIL clone with a distinct TCR recognized all four cancer cell lines restricted by HLA-B*4901. In a patient with bile duct cancer, two distinct antitumor cytolytic clones were isolated from a highly polyclonal CD8 + TIL repertoire. TCRs isolated from these clones recognized epitopes restricted by HLA-A*201. In a third patient, CD8 + TIL reactivity was progressively lost against an autologous colon cancer cell line that displayed loss of HLA haplotype. Conclusions: This study provides a basis for the development of immunotherapy for patients with advanced gastrointestinal malignancies by first establishing the presence of naturally occurring tumorreactive CD8 + TIL at the molecular level. Clin Cancer Res; 20(2); 331-43.

Original languageEnglish (US)
Pages (from-to)331-343
Number of pages13
JournalClinical Cancer Research
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Tumor-Reactive cd8<sup>+</sup> tcells in metastatic gastrointestinal cancer refractory to chemotherapy'. Together they form a unique fingerprint.

  • Cite this

    Turcotte, S., Gros, A., Tran, E., Lee, C. C. R., Wunderlich, J. R., Robbins, P. F., & Rosenberg, S. A. (2014). Tumor-Reactive cd8+ tcells in metastatic gastrointestinal cancer refractory to chemotherapy. Clinical Cancer Research, 20(2), 331-343. https://doi.org/10.1158/1078-0432.CCR-13-1736