PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy.

Checkpoint inhibition (CPI), particularly that targeting the inhibitory coreceptor programmed cell death protein 1 (PD-1), has transformed oncology. Although CPI can derepress cancer (neo)antigen-specific αß T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αß T cell recognition. In such settings, γδ T cells have been implicated, but the functional relevance of PD-1 expression by these cells is unclear. Here we demonstrate that intratumoral TRDV1 transcripts (encoding the TCRδ chain of Vδ1+ γδ T cells) predict anti-PD-1 CPI response in patients with melanoma, particularly those harboring below average neoantigens. Moreover, using a protocol yielding substantial numbers of tissue-derived Vδ1+ cells, we show that PD-1+Vδ1+ cells display a transcriptomic program similar to, but distinct from, the canonical exhaustion program of colocated PD-1+CD8+ αß T cells. In particular, PD-1+Vδ1+ cells retained effector responses to TCR signaling that were inhibitable by PD-1 engagement and derepressed by CPI.

First steps toward understanding the variability in acute pain service provision and the quality of pain relief in everyday practice across the United Kingdom.

BACKGROUND: Pain management for patients in hospital is a major problem. There is significant variation in care provision. Evidence is needed about the ways in which acute pain services are organized in order to understand whether these are linked to important differences in patient outcomes. The National Inpatient Pain Study group is a voluntary collaborative venture of inpatient pain specialists in the United Kingdom who are working toward establishing a national prospective database of service provision and activity. OBJECTIVES: The objectives of this article are (1) to describe current pain service provision and activity (2) to define and monitor the quality and side effects of the primary analgesic techniques, such as central neuraxial block or systemic analgesia, and identify variations in practice. METHODS: Phase 1: Surveys were conducted in two phases during 2010-2011. Information about the organization of services was collected from 121 centers via a live Website. Phase 2: The pilot clinical dataset was collected from 13 hospitals in 2011. RESULTS: Results indicated that staffing varied widely from one to nine nurses per hospital site. Twelve percent of hospitals did not routinely collect data. The main workload was orthopedic and general surgery based on data from 13 hospitals and 29,080 patients in 2011. Thirty-seven percent of patients reported a pain score of moderate to severe pain on the first assessment by the specialist pain team, and 21% reported severe pain. Nausea and vomiting was the most frequent adverse event reported. Sixty-nine major adverse events were logged, of which 64 documented respiratory depression (N = 29,080, 0.22%). CONCLUSIONS: Prospective longitudinal data has the potential to improve our understanding of variation in process and outcome measures and establish future research priorities.

Post-operative pain management: transition from epidural to oral analgesia.

Although managing pain in the acute surgical setting is a priority, there is a dearth of evidence to guide clinicians on how best to approach the discontinuation and transition of patients from epidural analgesia to oral analgesia post-operatively. This article describes an audit at a regional trust which examined data on patients' observations charts, as well as patients' self-reports of pain. The authors found that reducing epidural opioid concentrations post-operatively is useful in analgesic transition, using bupivacaine only for weaning has limited value, and that the timing of oral analgesia administration is important. They conclude that comprehensive pain assessment and better documentation are necessary to improve pain management practices. While the results demonstrate the advantage of reducing epidural opioid concentrations, decisions should be based on the needs of individual patients and not form part of a routine task.