The Dynamic Changes of Circulating Myeloid-Derived Suppressor Cells (MDSCs) Subsets in Colorectal Cancer Patients Undergoing Oxaliplatin-Based Chemotherapy.
Ralph Girson Gunarsa, Aru Wisaksono Sudoyo, Ricci Steven, Dilafitria Fauza, Fajar Lamhot Gultom, Ibrahim Basir, Dicky Kurniawan, Akterono Dwi Budiyati
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引用次数: 0
Abstract
Purpose: Increased level of circulating myeloid -derived suppressor cells (MDSCs) in colorectal cancer (CRC) patients has been associated with higher tumor stage and poorer survival due to poorer response to therapeutic agents. However, studies reported inconsistent results on how chemotherapeutic agents affecting the depletion of two major types of MDSCs, polymophonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). The present study aims to learn deeper on the dynamic changes of circulating MDSCs, especially in response to oxaliplatin-based treatment in CRC patients.
Methods: This was a prospective study that recruited 30 treatment-naive patients with varying stages of CRC who were scheduled to receive oxaliplatin-based chemotherapy. Blood sampling was conducted prior to and at several time points during and after chemotherapy. Multicolor flow cytometry assay was used to analyse the proportion of HLA-DR- and CD33+ with CD15+ (PMN-MDSCs) or CD14+ (M-MDSCs) cells within peripheral blood mononuclear cells (PBMCs). Other essential tumor biomarkers such as carcinoembryonic antigen (CEA) and tumor-infiltrating lymphocytes (TILs) were also assessed. As a control, 14 healthy subjects were recruited in this study.
Results: Indonesian treatment-naive CRC patients exhibited significantly higher circulating PMN-MDSCs compared to healthy subjects (p = 0.003), while M-MDSCs levels showed no significant difference between the groups (p = 0.890). Following chemotherapy, the MDSCs level demonstrated dynamic changes. Interestingly, a subgroup of CRC patients with decreased in both PMN- and M-MDSCs levels on D-14 of chemotherapy consistently showed a significant reduction in MDSCs levels during and after therapy completion compared to baseline (p = 0.0078).
Conclusions: Circulating MDSCs level, particularly PMN-MDSCs, in CRC patients, was significantly higher compared to healthy subjects. Changes in both circulating PMN- and M-MDSCs levels at D-14 chemotherapy might have prognostic value in oxaliplatin-based chemotherapy.
期刊介绍：
The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.
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