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

Abstract

Purpose

CD8⁺ 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 design

We applied a high-throughput TCR β-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.

Results

We 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 Vβ 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.

Conclusions

Although 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.

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