In vivo T-cell immune response against anaplastic lymphoma kinase in patients with anaplastic large cell lymphomas

Lorena Passoni, Barbara Gallo, Elia Biganzoli, Roberta Stefanoni, Maura Massimino, Massimo Di Nicola, Alessandro M. Gianni, Carlo Gambacorti-Passerini

Research output: Contribution to journalArticle

Abstract

Background and Objectives. Anaplastic lymphoma kinase (ALK) oncogenic fusion proteins, expressed in about 60% of anaplastic large cell lymphomas (ALCL), are tumor-specific molecular targets for such a malignancy. One of the promising ALK-targeted therapeutic options is cancer vaccination. In this study, we investigate whether ALK is a tumor-associated antigen suitable for immune interventions. Design and Methods. The frequency and the functional phenotype of the anti-ALK CDS precursor repertoire in freshly isolated peripheral blood mononuclear cells (PBMC) from healthy donors and ALK-positive patients were determined by major histocompatibility complex (MHC)/tetrameric analyses. The anti-ALK secondary immune responses were evaluated as PBMC-specific interferon (INF-γ) release by ELISPOT. In addition, the ability of the anti-ALK immune response to specifically lyse ALK-positive lymphoma cells was investigated by in vitro stimulation with ALK-derived peptide p280-89. Results. Tetrameric MHC/peptide complexes revealed high frequencies of CD8/ALK-tetramer-positive cells both in patients and in healthy individuals. However, the functional phenotype of the CD8/ALK-tetramer-positive lymphocytes showed the presence of effector and memory T lymphocytes only in patients. The anti-ALK cytotoxic T lymphocytes (CTL) of patients, but not healthy donors, displayed thresholds of activation comparable to those of CTL precursors of a recall antigen (influenza virus). A polyclonal ALK-specific tumor-reactive T-cell line was isolated from patients' peripheral blood lymphocytes. Interpretation and Conclusions. The presence of an anti-ALK effector/memory lymphocyte population in the peripheral blood of ALK-positive patients indicates an in vivo antigenic challenge. Thus, ALK is a lymphoma-associated antigen suitable for immune interventions. The high number of anti-ALK memory CD8 T cells present in patients' PBMC may represent a valid source of activated CTL suitable for cancer cell lysis.

Original languageEnglish
Pages (from-to)48-55
Number of pages8
JournalHaematologica
Volume91
Issue number1
Publication statusPublished - Jan 2006

Keywords

  • ALCL
  • ALK
  • Cancer vaccine
  • Immunotherapy
  • Tumor antigen

ASJC Scopus subject areas

  • Hematology

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