Academic Journal
Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients
| العنوان: | Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients |
|---|---|
| المؤلفون: | Muraro, Elena, Del Ben, Fabio, Turetta, Matteo, Cesselli, Daniela, Bulfoni, Michela, Zamarchi, Rita, Rossi, Elisabetta, Spazzapan, Simon, Dolcetti, Riccardo, Steffan, Agostino, Brisotto, Giulia |
| المساهمون: | Ministero della Salute |
| المصدر: | Frontiers in Oncology ; volume 12 ; ISSN 2234-943X |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2022 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Background Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC. Methods A cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita’s overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher’s, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method. Results Stratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fonc.2022.983887 |
| DOI: | 10.3389/fonc.2022.983887/full |
| الاتاحة: | http://dx.doi.org/10.3389/fonc.2022.983887 https://www.frontiersin.org/articles/10.3389/fonc.2022.983887/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.802E7716 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fonc.2022.983887 |
|---|