Background:Regulatory T cells (Treg) are enriched in human colorectal cancer (CRC) where they suppress anti-tumour immunity. The chemokine receptor CCR5 has been implicated in the recruitment of Treg from blood into CRC and tumour growth is delayed in CCR5−/− mice, associated with reduced tumour Treg infiltration.Methods:Tissue and blood samples were obtained from patients undergoing resection of CRC. Tumour-infiltrating lymphocytes were phenotyped for chemokine receptors using flow cytometry. The presence of tissue chemokines was assessed. Standard chemotaxis and suppression assays were performed and the effects of CCR5 blockade were tested in murine tumour models.Results:Functional CCR5 was highly expressed by human CRC infiltrating Treg and CCR5high Treg were more suppressive than their CCR5low Treg counterparts. Human CRC-Treg were more proliferative and activated than other T cells suggesting that local proliferation could provide an alternative explanation for the observed tumour Treg enrichment. Pharmacological inhibition of CCR5 failed to reduce tumour Treg infiltration in murine tumour models although it did result in delayed tumour growth.Conclusions:CCR5 inhibition does not mediate anti-tumour effects as a consequence of inhibiting Treg recruitment. Other mechanisms must be found to explain this effect. This has important implications for anti-CCR5 therapy in CRC.

Objectives To determine whether preoperative dexamethasone reduces postoperative vomiting in patients undergoing elective bowel surgery and whether it is associated with other measurable benefits during recovery from surgery, including quicker return to oral diet and reduced length of stay. Design Pragmatic two arm parallel group randomised trial with blinded postoperative care and outcome assessment. Setting 45 UK hospitals. Participants 1350 patients aged 18 or over undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology. Interventions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia compared with standard care. Main outcome measures Primary outcome: reported vomiting within 24 hours reported by patient or clinician. Secondary outcomes: vomiting with 72 and 120 hours reported by patient or clinician; use of antiemetics and postoperative nausea and vomiting at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120 hours or discharge and at 30 days; time to return to fluid and food intake; length of hospital stay; adverse events. Results 1350 participants were recruited and randomly allocated to additional dexamethasone (n=674) or standard care (n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22; P=0.003). Additional postoperative antiemetics were given (on demand) to 265 (39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to 72 hours. There was no increase in complications. Conclusions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly reduces both the incidence of postoperative nausea and vomiting at 24 hours and the need for rescue antiemetics for up to 72 hours in patients undergoing large and small bowel surgery, with no increase in adverse events. Trial registration EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).

No abstract