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

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 ß-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 Vß 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.

[Clinical analysis of 33 cases of primary esophageal small cell carcinoma].

BACKGROUND & OBJECTIVE: Esophagus is the most commonly involved site of extrapulmonary small cell carcinoma. However, no standard treatment has been established for primary esophageal small cell carcinoma. This study was to summarize the clinical characteristics, treatment, and prognosis of primary esophageal small cell carcinoma, and explore the impact of chemotherapy on the survival. METHODS: The records of 33 patients with primary esophageal small cell carcinoma, treated in Cancer Center of Sun Yat-sen University from Jan. 1985 to Dec. 2005, were reviewed to summarize the clinical characteristics and impact of therapy modality on the survival. Prognostic factors were analyzed by Kaplan-Meier and log-rank method. RESULTS: The median survival time of the 33 patients was 11.3 months; the 1-, 3-, and 5-year survival rates were 45.1%, 16.6%, and 3.5%, respectively. Clinical stage was the most important prognostic factor. The median survival time of the patients received local treatment (surgical operation or radiotherapy) was 6.3 months; the 1-, 2-, 3-year survival rates were 31.1%, 23.5%, and 8.2%, respectively. The median survival time of the patients received local treatment plus chemotherapy was 15.4 months; the 1-, 2-, 3-year survival rates were 69.3%, 34.6%, and 28.7%, respectively. CONCLUSION: Surgical operation plus chemotherapy can improve the survival of the patients with early stage primary esophageal small cell carcinoma.