Abstract
BackgroundEarly detection of capecitabine-resistance could largely increase overall survival of colorectal cancer (CRC) patients. Previous studies suggested examination of immune cells in peripheral blood would help to predict efficacy of chemotherapy.MethodsWe examined the immunological characteristics of peripheral blood in CRC patients with capecitabine treatment. We analyzed the relationships between the abnormal immune cell population in capecitabine-resistance patients and major clinical features. Furthermore, RNA sequencing, analyses of cell surface marker expression and the correlations with other major immune cell populations were performed using this population to explore the possible function of these cells.ResultsThe expression level of CD16 on neutrophils was down-regulated in capecitabine-resistant CRC patients. Patients with CD16low/−neutrophils after capecitabine therapy had adverse clinical features. What’s important, the change of CD16 expression level on neutrophils appeared much earlier than CT scan. RNA sequencing revealed that CD16low/−neutrophils in capecitabine-resistant patients had lower expression level of neutrophil-related genes, compared to CD16+neutrophils in capecitabine-sensitive patients, suggesting this CD16low/−population might be immature neutrophils. Furthermore, the expression level of CD16 on neutrophils in patients with capecitabine treatment was positively correlated with the number of anti-tumor immune cell subsets, such as CD8+T cell, CD4+T cell, NK cell and monocyte.ConclusionsOur findings indicated that CD16 expression on neutrophils in peripheral blood was a good prognostic marker for predicting efficacy of capecitabine in CRC patients.
Highlights
Detection of capecitabine-resistance could largely increase overall survival of colorectal cancer (CRC) patients
We discovered that the expression of CD16 on CD11b+myeloid cells was dramatically decreased in capecitabine-resistant CRC patients after capecitabine adjuvant therapy
CD16 expression levels on CD11b+myeloid cells in peripheral blood of capecitabine-resistant CRC patients are different from capecitabine-sensitive CRC patients after capecitabine therapy
Summary
Detection of capecitabine-resistance could largely increase overall survival of colorectal cancer (CRC) patients. Colorectal cancer (CRC) is one of the leading cause of death worldwide. More than 1.8 million patients are diagnosed with CRC every year [1,2,3]. What’s more, this lifethreaten disease kills nearly 0.9 million people annually [1]. In north America and Europe, the morbidity and mortality remain at high level [1], despite developments of cancer screening and endoscopy [2, 3]. In China, CRC becomes the 5th most diagnosed cancer and 5th most deadly cancer [4,5,6]. 0.4 million new cases are diagnosed and about 0.2 million people die from the disease every year [6]
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