T-Cell Receptor Sequencing Reveals Novel Biomarkers For Ovarian Cancer

Deep T-cell receptor (TCR) sequencing has been used to evaluate the clonal composition of tumor-infiltrating lymphocytes and identify novel prognostic biomarkers in ovarian cancer.

The ability of tumor-infiltrating lymphocytes (TILs) such as T-cells to produce multitudes of clones that overwhelm and effectively control cancer cells has been demonstrated, but the significance of the composition of T-cell repertories is unknown.

Scientists at Roswell Park Cancer Institute (Buffalo, NY, USA) analyzed 198 blood samples from 99 women with ovarian cancer using the ImmunoSEQ platform (Adaptive Biotechnologies, South San Francisco, CA, USA). Spontaneous immune responses were assessed by measuring serum antibodies against ovarian cancer-associated antigens, such as NY-ESO-1, that are not expressed in normal body tissues, but are expressed in cancers. The degree of CD3+ and CD8+T-cell infiltration was evaluated by immunohistochemistry.

The team found 10.3 million unique clones in peripheral blood and 1.4 million unique clones in tumors. Poor overall survival was associated with higher T-cell diversity, that is, higher clone-to-TIL ratios. While higher TIL levels conferred a favorable prognosis in patients with spontaneous immune response to tumor antigens, they were a poor prognostic factor in patients who did not experience an immune response.

The authors concluded that the integration of T-cell repertoire diversity in tumor and peripheral blood with density of TILs identified clone/CD3 TIL and clone/CD4 TIL ratios; TIL clonality; and the degree of overlap of peripheral and TIL repertoire as novel prognostic biomarkers in ovarian cancer. The presence of pre-existing anti-tumor immunity shapes the correlation of TIL clonality and peripheral/TIL overlap with clinical outcome.

Kunle Odunsi, MD, PhD, a Professor of Gynecologic Oncology, and lead author of the study said, “While the presence of lymphocytes in tumors is often associated with better clinical outcomes, this study adds clarity on the diversity of T cells within the tumor environment and their influence on ovarian cancer outcomes.” The study was presented on June 6, 2016, at the American Society of Clinical Oncology (ASCO) 52nd Annual Meeting held in Chicago, IL, USA.

Related Links:
Roswell Park Cancer Institute
Adaptive Biotechnologies