CD16 expression on neutrophils predicts treatment efficacy of capecitabine in colorectal cancer patients

BACKGROUND: Early 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. METHODS: We 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. RESULTS: The expression level of CD16 on neutrophils was down-regulated in capecitabine-resistant CRC patients. Patients with CD16(low/−)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 CD16(low/−)neutrophils in capecitabine-resistant patients had lower expression level of neutrophil-related genes, compared to CD16(+)neutrophils in capecitabine-sensitive patients, suggesting this CD16(low/−)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. CONCLUSIONS: Our findings indicated that CD16 expression on neutrophils in peripheral blood was a good prognostic marker for predicting efficacy of capecitabine in CRC patients.