Lídia Maria Rebolho Batista Arantes

AIMS: Catheter ablation of long-lasting persistent atrial fibrillation (AF) has been performed with varying results using a combination of different techniques. Whether arrhythmia termination during ablation is associated with an improved clinical outcome is controversial. METHODS AND RESULTS: In this prospective study, 153 consecutive patients (56 +/- 10 years) underwent catheter ablation of persistent AF (25 +/- 33 months) using a stepwise approach with the desired procedural endpoint being AF termination. Repeat ablation was performed for patients with recurrent AF or atrial tachycardia (AT) after a 1 month blanking period. A minimum follow-up of 12 months with repeated Holter monitoring was performed. Atrial fibrillation was terminated in 130 patients (85%). There was a lower incidence of AF in those patients in whom AF was terminated during the index procedure compared with those who had not (5 vs. 39% P < 0.0001, mean follow-up 32 +/- 11 months). Seventy-nine patients underwent repeat procedures: 64/130 in the termination group (6 AF, 58 AT) and 15 in the non-termination group (9 AF, 7 AT). After repeat ablation, sinus rhythm was maintained in 95% in whom AF was terminated compared with 52% in those in whom AF could not be terminated. CONCLUSION: Procedural termination of long-lasting AF by catheter ablation alone is associated with an improved outcome.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) encompasses tumors arising from several locations (oral and nasal cavities, paranasal sinuses, salivary glands, pharynx, and larynx) and currently stands as the sixth most common cancer worldwide. The most important risk factors identified so far are tobacco and alcohol consumption, and, for a subgroup of HNSCCs, infection with high-risk types of human papillomavirus (HPV). Despite several improvements in the treatment of these tumors in the last decades, overall survival rates have only improved marginally, mainly due to the advanced clinical stage at diagnosis and the high rates of treatment failure associated with this late diagnosis. Areas covered: This review will focus on the feasibility of evaluating molecular-based biomarkers (mRNA, microRNA, lncRNA, DNA methylation and protein expression) in body fluids (serum, plasma, and saliva) as markers for diagnosis, prognosis, and surveillance. Expert commentary: The potential use of those markers in the clinical setting would allow for early diagnosis, prediction of treatment response, improvement in treatment selection and provide disease monitoring for early detection of tumor recurrence. It can ultimately be translated into better survival rates and improved quality of life for HNSCC patients.

Objective To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity. Design We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial. Results We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13 + tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens. Conclusion We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.