Transcriptional analysis of tumor-specific T-cell responses in cancer patients

Dirk Nagorsen, Ena Wang, Francesco M. Marincola, Jos Even

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Over the last decade, tumor immunology in general and tumor immunotherapy in particular have made important progress. Thanks to the discovery of tumor-associated antigens (TAA), and the consequent development of active-specific immunization protocols, TAA-specific T-cell responses can now be induced reproducibly in cancer patients. However, clinical responses directly ascribable to TAAT-specific T cells occur only occasionally. It is not clear why TAA-specific T cells do not eliminate tumor cells in vivo. This paradoxical coexistence of antigen-bearing tumor cells and antigen-specific T cells constitutes a critical point of current investigation. In recent years, protein-ligand interaction-based methods aimed at the identification and characterization of T cells using antibodies (cell surface phenotyping, intracellular and secreted cytokine detection), or HLA-peptide multimers, have significantly improved the analysis of TAA-specific T cells. These methods, however, seem to have reached the limit of their usefulness. Transcriptional analysis may add sensitivity and resolution and may provide global pictures of the multifactorial requirements for an efficient immune response against tumors. In this review, we describe the use of molecular genetic methods, such as real time qRT-PCR, cDNA microarrays, and TCR repertoire analysis. In addition, we describe techniques for high-fidelity messenger RNA amplification that allow high-throughput analysis of samples obtained from minimal sources, such as HLA/ peptide tetramer sorted antigen-specific T cells, laser capture dissection, or fine needle aspirates. Recent work discussed in this review summarizes the complementarity of transcriptional analysis as an essential tool that, in addition to conventional methods, may deepen and broaden the characterization of tumor-specific T cells.

Original languageEnglish
Pages (from-to)449-462
Number of pages14
JournalCritical Reviews in Immunology
Volume22
Issue number5-6
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Neoplasm Antigens
T-Lymphocytes
Neoplasms
Antigens
Peptides
Allergy and Immunology
Oligonucleotide Array Sequence Analysis
Immunotherapy
Needles
Dissection
Real-Time Polymerase Chain Reaction
Molecular Biology
Vaccination
Lasers
Cytokines
Ligands
Messenger RNA
Antibodies
Proteins

Keywords

  • cDNA microarrays
  • qRT-PCR
  • Specific T cells
  • TCR repertoire analysis

ASJC Scopus subject areas

  • Immunology

Cite this

Transcriptional analysis of tumor-specific T-cell responses in cancer patients. / Nagorsen, Dirk; Wang, Ena; Marincola, Francesco M.; Even, Jos.

In: Critical Reviews in Immunology, Vol. 22, No. 5-6, 2002, p. 449-462.

Research output: Contribution to journalReview article

Nagorsen, D, Wang, E, Marincola, FM & Even, J 2002, 'Transcriptional analysis of tumor-specific T-cell responses in cancer patients', Critical Reviews in Immunology, vol. 22, no. 5-6, pp. 449-462.
Nagorsen, Dirk ; Wang, Ena ; Marincola, Francesco M. ; Even, Jos. / Transcriptional analysis of tumor-specific T-cell responses in cancer patients. In: Critical Reviews in Immunology. 2002 ; Vol. 22, No. 5-6. pp. 449-462.
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