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Tumor-infiltrating T lymphocyte clonality predicts prognosis in human ovarian cancer
  1. Takemasa Tsuji1,
  2. Kevin H Eng2,
  3. Sacha Gnjatic3,
  4. Junko Matsuzaki1,
  5. Rachel Brightwell4,
  6. Anthony Miliotto1,
  7. Ryan Emerson5,
  8. Cindy Desmarais5,
  9. Erika Lindsley5,
  10. Julie Rubinstein5,
  11. Jianmin Wang2,
  12. Song Liu2,
  13. Harlan Robins5 and
  14. Kunle Odunsi1,4
  1. Aff1 grid.240614.50000000121818635Center for ImmunotherapyRoswell Park Cancer Institute Buffalo NY USA
  2. Aff2 grid.240614.50000000121818635Biostatistics and BioinformaticsRoswell Park Cancer Institute Buffalo NY USA
  3. Aff3 grid.59734.3c0000000106702351Tisch Cancer InstituteIcahn School of Medicine at Mount Sinai New York NY USA
  4. Aff4 grid.240614.50000000121818635Gynecologic OncologyRoswell Park Cancer Institute Buffalo NY USA
  5. Aff5 grid.421940.aAdaptive Biotechnologies Seattle WA USA

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Meeting abstracts


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.


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.


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.


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.