Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 67, Issue 11, Pages 1743-1752Publisher
SPRINGER
DOI: 10.1007/s00262-018-2213-1
Keywords
Breast cancer; CD8(+) T-cell repertoire; HER2 expression status; Clinical response
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Funding
- National Natural Science Foundation of China [81402255]
- Guangdong Province Natural Science Funds for Distinguished Young Scholar [2016A030306050]
- Guangdong Province Natural Science Funds [2014A030313803]
- Science and Technology Innovation Platform in Foshan City [2015AG10002]
- Guangdong Te Zhi Program youth science and technology talent project [2015TQ01R462]
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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.
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