Abstract
The immune system and inflammation plays a significant role in tumour immune evasion enhancing disease progression and reducing survival in colorectal cancer (CRC). Patients with advanced stages of colorectal cancer will all undergo treatment with cytotoxic chemotherapy which may alter the complexity of immune cell populations. This study used mass cytometry to investigate the circulating immune cell profile of advanced CRC patients following acute and chronic doses of standard cytotoxic chemotherapy and analysed seven major immune cell populations and over 20 subpopulations. Unsupervised clustering analysis of the mass cytometry data revealed a decrease in NK cells following one cycle of cytotoxic chemotherapy. Investigation into the NK sub-population revealed a decline in the CD56dim CD16+ NK cell population following acute and chronic chemotherapy treatment. Further analysis into the frequency of the NK cell sub-populations during the long-term chemotherapy treatment revealed a shift in the sub-populations, with a decrease in the mature, cytotoxic CD56dim CD16+ accompanied by a significant increase in the less mature CD56dim CD16− and CD56bright NK cell populations. Furthermore, analysis of the phosphorylation status of signalling responses in the NK cells found significant differences in pERK, pP38, pSTAT3, and pSTAT5 between the patients and healthy volunteers and remained unchanged throughout the chemotherapy. Results from this study reveals that there is a sustained decrease in the mature CD16+ NK cell sub-population frequency following long-term chemotherapy which may have clinical implications in therapeutic decision making.
Highlights
An estimated 1.4 million people are annually diagnosed with colorectal cancer (CRC) making it the third most common cancer in the world [1]
We have used mass cytometry to enhance our understanding of the immune profile of advanced CRC patients undergoing standard cytotoxic chemotherapy
The unsupervised clustering analysis of our high-dimensional data following an acute dose of chemotherapy revealed a decrease in cluster 14, identified as Natural Killer (NK) cells
Summary
An estimated 1.4 million people are annually diagnosed with colorectal cancer (CRC) making it the third most common cancer in the world [1]. For people with locally advanced or metastatic CRC, combination cytotoxic chemotherapy is the backbone to all chemotherapy regimens, which primarily involves 5-fluorouracil (5-FU), folinic acid (leucovorin), and either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) [2, 3]. With the advances in molecular targeted therapies, metastatic CRC has benefited from the addition of molecular targeted drugs, such as EGFR or VEGF inhibitors, cetuximab and bevacuzimab, respectively [4, 5]. These targeted agents have extended the median long-term survival to almost 3 years for people with metastatic CRC [4]. Further improvements in survival will require new drug targets to be identified
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
