Skip to content

Advertisement

  • Poster presentation
  • Open Access

Tumor-infiltrating T lymphocyte clonality predicts prognosis in human ovarian cancer

  • 1,
  • 2,
  • 3,
  • 1,
  • 4,
  • 1,
  • 5,
  • 5,
  • 5,
  • 5,
  • 2,
  • 2,
  • 5 and
  • 1, 4
Journal for ImmunoTherapy of Cancer20131 (Suppl 1) :P64

https://doi.org/10.1186/2051-1426-1-S1-P64

  • Published:

Keywords

  • Ovarian Cancer
  • Cell Clonality
  • Freeze Tumor Tissue
  • Sequence Base Analysis
  • Preferential Infiltration

Background

The prognostic significance of the number of tumor-infiltrating T cells has been demonstrated for many tumor types. In contrast, the significance of the tumor-infiltrating T cell clonality, which reflects the preferential infiltration or expansion of T cell clones in the tumor microenvironment, has not been clear because of the technical hurdles required for evaluating each T cell clone in the tumor. In order to delineate the complexity of T cell responses and define correlates of a protective immunity, we applied a recently developed deep T cell receptor (TCR)-sequencing technology (immunoSEQ) to paired frozen tumor tissues and peripheral blood mononuclear cells from 99 ovarian cancer patients.

Methods

Rearranged β TCR chain DNA sequences were sequenced using immunoSEQ technology. Frequency of each T cell clone was obtained from the copy number of the sequence. T cell clonality of the specimens was calculated from entropy of TCR sequences. Spontaneous immune responses against tumor-associated antigens (NY-ESO-1, MAGE-A1, MAGE-A3 and p53) were evaluated by measuring serum antibodies by ELISA.

Results

Approximately 3(±3)×106and 4(±2)×106 full-length TCR beta chain sequences were obtained corresponding to the detection limit for T cell frequency at 3×10-7and 2×10-7 for tumor and blood samples, respectively. In patients who had spontaneous antibodies against a panel of tumor-associated antigens, more clonal T cell infiltration was associated with longer progression-free survival. In sharp contrast, clonal infiltration was a worse prognostic factor in patients without detectable humoral immune responses against surrogate tumor antigens. From sequence based analyses, we found a set of shared TCR sequences among patients.

Conclusion

Deep TCR sequencing using immunoSEQ technology is a powerful tool to characterize tumor-infiltrating T cell clonality using frozen tumor tissues. Our analyses indicate that evaluation for spontaneous anti-tumor immune responses is required to correctly understand the prognostic significance of tumor-infiltrating T cells.

Authors’ Affiliations

(1)
Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA
(2)
Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA
(3)
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
(4)
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA
(5)
Adaptive Biotechnologies, Seattle, WA, USA

Copyright

© Tsuji et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement