Kai-Rong Lin1, Dan-Mei Pang2, Ya-Bin Jin1, Qian Hu2, Ying-Ming Pan1, Jin-Huan Cui1, Xiang-Ping Chen1, Yin-Xin Lin2, Xiao-Fan Mao1, Hai-Bo Duan2, Wei Luo3. 1. Clinical Research Institute, First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), NO. 81 North of Lingnan Avenue, Foshan, 528000, Guangdong, China. 2. Department of Breast Oncology, Cancer Center, First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, 528000, Guangdong, China. 3. Clinical Research Institute, First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), NO. 81 North of Lingnan Avenue, Foshan, 528000, Guangdong, China. luowei@fsyyy.com.
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.
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 cancerpatients 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 cancerpatients. 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 cancerpatients 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.
Entities:
Keywords:
Breast cancer; CD8+ T-cell repertoire; Clinical response; HER2 expression status
Authors: Ainhoa Arana Echarri; Mark Beresford; John P Campbell; Robert H Jones; Rachel Butler; Kenneth J Gollob; Patricia C Brum; Dylan Thompson; James E Turner Journal: Front Immunol Date: 2021-02-01 Impact factor: 7.561
Authors: Boris I Chobrutskiy; Michelle Yeagley; Andrea Diviney; Saif Zaman; Etienne C Gozlan; Price Tipping; Darush M Koohestani; Andrea M Roca; George Blanck Journal: Immunology Date: 2020-01-21 Impact factor: 7.397