A large cohort study of peripheral blood T-cell receptor (TCR) clonotype diversity in patients with breast cancer diagnosed with either ductal carcinoma in situ or de novo stage IV disease has found that the diversity of T cells is associated with age and intratumor immune status and might be linked to the probability of disease progression. The results highlight the importance of peripheral immunity and age in tumor evolution and suggest further exploration of blood TCR as a biomarker of disease progression in larger patient cohorts, according to the study authors. The study by Nishida et al was published in the Proceedings of the National Academy of Sciences.
Study Methodology
Researchers from Dana-Farber Cancer Institute assessed the peripheral blood TCR clonotype in blood samples of 485 patients with newly diagnosed stage 0 ductal carcinoma in situ (DCIS) or de novo stage IV breast cancer at younger (< 45) or older (≥ 45) age. The patients were participants in the Young Women’s Breast Cancer Study and the EMBRACE cohort study. The researchers also performed RNA sequencing on whole blood and DCIS tumor tissues in a subset of patients to analyze how the transcriptome of peripheral blood and tumor tissue relates to TCR diversity.
Results
The researchers found that TCR clonotype diversity was significantly lower in older compared to younger patients with breast cancer regardless of tumor stage at diagnosis. In the younger age group, TCR-α clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, patients with higher TCR-α clonotype diversity were more likely to have a recurrence compared to those with lower diversity.
Whole-blood transcriptome profiles were distinct depending on the TCRα Chao1 diversity score. There were more CD8-positive T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-α Chao1 diversity than in those with lower diversity.
“Our results highlight the importance of peripheral immunity and age in tumor evolution and suggest further exploration of TCR diversity as a biomarker of disease progression in larger patient cohorts,” concluded the study authors.
Simona Cristea, PhD; Franziska Michor, PhD; and Kornelia Polyak, MD, PhD, all of Dana-Farber Cancer Institute, are the corresponding authors of the study.
Disclosure: Funding for this study was provided by the National Cancer Institute, Dana-Farber/Harvard Cancer Center SPORE P50CA168504, The Breast Cancer Research Foundation, Susan G. Komen, the American Cancer Society, Louise Sandberg Fund, and the Ludwig Center at Harvard. For full disclosures of the study authors, visit pnas.org.
