TCR Repertoire as a Novel Indicator for Immune Monitoring and Prognosis Assessment of Patients With Cervical Cancer.

There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy.

Urinary fibronectin as a predictor of a residual tumour load after transurethral resection of bladder transitional cell carcinoma.

OBJECTIVE: To determine whether the level of urinary fibronectin predicts the residual tumour load after transurethral resection (TUR) of bladder transitional cell carcinoma (TCC). PATIENTS AND METHODS: Urine samples were collected from 167 consecutive patients with suspected bladder cancer admitted for TUR. Samples were taken both before and after surgery. Bladder tumour fibronectin (BTF) was analysed using a solid-phase chemiluminescent immunometric test. Creatinine in urine was also determined and the BTF/creatinine ratio calculated. RESULTS: Patients were divided into a control group of 41 whose previous diagnosis was negative for BT and another of 126 with a positive diagnosis for BT, which was further subdivided into those with and without residual tumour, according to findings from specimens obtained during the second procedure (repeat TUR or cystectomy). After the second procedure, 68 patients (56%) had no residual tumour, whereas 54 (44%) did. Four patients with BT who did not have the second procedure were excluded from the study. The median BTF and BTF/creatinine value in the control group was 33.2 microg/L and 51.4 microg/g, respectively, before the first TUR, and 29.6 microg/L and 46.7 microg/g, respectively, after the first TUR. There were no statistically significant changes in BTF and BTF/creatinine ratio (P = 0.61 and 0.79, respectively). In the group with TCC, the BTF decreased from 211.9 to 97.3 microg/L (P = 0.02) and the BTF/creatinine ratio from 281.6 to 146.5 microg/g (P = 0.009) for those with residual tumour, while it decreased from 195.1 to 34.0 microg/L (P = 0.007) and the BTF/creatinine ratio decreased from 249.1 to 53.7 microg/g (P = 0.003) for those with no residual tumour. After initial TUR, the patients with residual tumour had significantly greater levels of BTF and BTF/creatinine than did those with no residual tumour (P = 0.004 and 0.006, respectively). The receiver operating characteristic curves showed an optimum threshold of 67.8 microg/L and 81.3 microg/g for BTF and the BTF/creatinine in detecting residual tumour, respectively, with a sensitivity of 91.4% and 89.0%, respectively, and a specificity of 87.8% and 85.6%, respectively. CONCLUSION: Urinary fibronectin, in addition to being one of the best markers for diagnosing bladder carcinoma, can be used to determine the presence of residual tumour load after TUR of bladder TCC.