Circulating CD8+ T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients
| Autor: | Xiang-Ping Chen, Mao Xiaofan, Haibo Duan, Kai-Rong Lin, Danmei Pang, Qian Hu, Wei Luo, Yin-Xin Lin, Jin-Huan Cui, Jin Yabin, Pan Yingming |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Chemotherapy business.industry medicine.medical_treatment Repertoire Immunology T-cell receptor Cancer medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system Breast cancer Oncology 030220 oncology & carcinogenesis medicine Cancer research Immunology and Allergy Cytotoxic T cell business CD8 |
| Zdroj: | Cancer Immunology, Immunotherapy. 67:1743-1752 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-018-2213-1 |
| Popis: | 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. 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. 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. 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. |
| Databáze: | OpenAIRE |
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