TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination.

Abstract

Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.

• Authors: Melody Hsu, Shaina Sedighim, Tina Wang, Joseph P Antonios, Richard G Everson, Alexander M Tucker, Lin Du, Ryan Emerson, Erik Yusko, Catherine Sanders, Harlan S Robins, William H Yong, Tom B Davidson, Gang Li, Linda M Liau, Robert M Prins
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 4 Issue 5 Pg. 412-418 (05 2016) ISSN: 2326-6074 [Electronic] United States
• PMID: 26968205 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Brain Neoplasms (immunology, therapy)
• Dendritic Cells (transplantation)
• Disease Progression
• Glioblastoma (immunology, therapy)
• Humans
• Immunotherapy, Adoptive (methods)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Receptors, Antigen, T-Cell (blood, metabolism)
• Survival Analysis
• Vaccination (methods)