Giulia Gallerani, Junior Assistant Professor at Alma Mater Studiorum – University of Bologna, posted on LinkedIn about recent paper she and her colleagues co-authored:
“New Publication in Cell Death and Disease!
I’m very pleased to present our new study on circulating tumor cells (CTCs) and their interaction with the immune system. Tumor dissemination is a crucial step in cancer progression, yet the role of the immune system in supporting CTC survival and proliferation remains largely unknown.
In our study, we developed an in vitro co-culture system combining CTCs and immune cells from the same patient, improving the success rate in establishing long-term CTC-derived cell lines. This approach allowed us to characterize the interactions between cancer and immune cells, focusing on cytokines and extracellular vesicles(EVs).
Key findings
- Four CRC-derived cell lines were successfully established from patients with metastatic gastroesophageal cancer, maintained in culture for over a year, and characterized at the genetic and molecular levels.
- Identification of common chromosomal alterations, including MYC amplification(8q24.21) and CDKN2A/B deletion (9p21.3), impacting immune response regulation.
- CTC-derived cell lines exhibited distinct transcriptomic profiles compared to primary tumors, with activation of E2F,G2M,and MYC pathways and downregulation of the interferon response.
- In vivo zebrafish experiments revealed that the most invasive CTC cell lines shared a mutation in RAB14
- CTC-derived EVs carried microRNAs targeting YAP, BRG1-AKT1, and TCF8-HDAC pathways, suggesting a crucial communication mechanism that enhances CTC survival and dissemination.
These findings reinforce the role of the immune system in supporting CTC proliferation through EV-mediated signaling and highlight how the genomic and transcriptomic alterations of CTCs may make them less visible to the immune system, facilitating their survival and spread to distant sites.
I hope this work paves the way for new insights into understanding and counteracting tumor dissemination!
Gastroesophageal circulating tumor cell crosstalk with peripheral immune system guides CTC survival and proliferation
Authors: Tania Rossi, Giulia Gallerani, et al.
