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. Roswell Park Cancer Institute (RPCI) researchers used deep T-cell receptor (TCR) sequencing to evaluate the clonal composition of TILs and identify novel prognostic biomarkers in ovarian cancer. The findings will be presented at the American Society of Clinical Oncology (ASCO) 52nd Annual Meeting in Chicago.
To define the impact of an inventory of TILs on antitumor immunity, researchers analyzed 198 blood samples from 99 women with ovarian cancer using the ImmunoSEQ platform. 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 TILs infiltration also was evaluated by immunohistochemistry.
The Roswell Park 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.
"While the presence of lymphocytes in tumors is often associated with better clinical outcomes, this research adds clarity on the diversity of T cells within the tumor environment and their influence on ovarian cancer outcomes," says first author Kunle Odunsi, MD, PhD, FRCOG, FACOG, Deputy Director, M. Steven Piver Professor and Chair of Gynecologic Oncology, and Executive Director of the Center for Immunotherapy at Roswell Park.
"This study also adds greater understanding of tumor-infiltrating lymphocytes and their influence on the causes and progression of ovarian cancer. The overlap and density of these lymphocytes within the tumor and peripheral blood offer novel prognostic biomarkers for this deadly disease," adds Richard Koya, MD, PhD, Associate Director of the Roswell Park Center for Immunotherapy and Director of the Institute's Vector Development and Production Facility.
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