Circulating CD8+ T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients

PurposeCD8(+) T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8(+) T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy.Experimental designWe applied a high-throughput TCR -chain sequencing method to characterize the CD8(+) T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8(+) T-cell repertoire during chemotherapy were analyzed.ResultsWe found that the HEC ratios of the CD8(+) T-cell repertoires from HER2(+) breast cancer patients were significantly higher than those of HER2(-) patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8(+) T cells. Several V and CDR3 motifs preferentially used in HER2(+) patients were identified. Besides, we found that the circulating CD8(+) T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8(+) T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response.ConclusionsAlthough functional studies of clonally expanded CD8(+) T-cell populations are clearly required, our results suggest that the circulating CD8(+) T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.