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

ABSTRACT: 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 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. 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.

SUBMITTER: Lu Y

PROVIDER: S-EPMC7414545 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Lu Yu Y Huang Yizhou Y Huang Lei L Xu Yanjie Y Wang Zien Z Li Han H Zhang Ting T Zhong Ming M Gao Wei-Qiang WQ Zhang Yan Y

BMC immunology 20200808 1

<h4>Background</h4>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.<h4>Methods</h4>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 an ...[more]

PMID: 32770940

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Project description:Patients exhibiting pancreatic cancer possess poor rates of survival. Therefore, the identification of a biomarker that can be measured non-invasively and be used to predict patient outcomes is required for the successful treatment of pancreatic cancer. The present study evaluated serum microRNA (miRNA/miR) profiles in patients exhibiting pancreatic cancer, who were treated with lapatinib and capecitabine in a phase II trial. Serum samples were collected for the measurement of a panel of miRNAs (miR-21, miR-210, miR-221 and miR-7) associated with the epidermal growth factor receptor (EGFR)1 and human epidermal growth factor receptor (HER)2 pathways. Preclinically, human pancreatic cancer PANC-1, MIA PaCa-2 and BXCP-3 cell lines were utilized for miRNA and drug resistance studies. In total, 6/17 patients treated experienced disease progression following 2 cycles of treatment [non-responders (NRS)], while another 6/17 patients exhibited a stable disease state and received >4 cycles of treatment [responders (RS); range, 4-22 cycles]. Five patients withdrew from the study due to severe toxicity or mortality. The mean overall survival time was 6.5 vs. 10.4 months for NRS and RS, respectively. Significant upregulation of serum miRNAs at earlier time points (3-6 weeks) was observed in NRS. miRNA levels increased with cancer progression, and lapatinib and 5-fluorouracil (5-FU; the active form of capecitabine) treatment increased the miRNA levels (specifically miR-210 and miR-221) in the treatment-resistant pancreatic cancer PANC-1 and MIA PaCa-2 cell lines. However, lapatinib and 5-FU treatment did not increase the miRNA levels in the treatment-sensitive BXPC-3 cell line. Inhibition of miR-221 increased the sensitivity of the PANC-1 cells to treatment. In conclusion, an increase in specific serum miRNAs was associated with resistance to lapatinib and capecitabine treatment. Additional investigation is required with regard to the application of the miRNA panel investigated in the present study as a potential predictor of patient responses to anti-EGFR/HER2 treatment.

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

Publications

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

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