Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Accuracy of medical directors for indirect medical oversight on prehospital care

Objective@#This study aimed to evaluate the accuracy of the assessment of medical directors for indirect medical oversight on prehospital care. @*Methods@#Medical directors assessed the same prehospital care run sheets with six cases of cardiac arrest, four cases of withholding or interruption of cardiopulmonary resuscitation (CPR) and six cases of severe trauma patients. Demographics of the medical directors and the accuracy of their assessment for the prehospital care run sheets were investigated. @*Results@#Board certified emergency physician was 14 of the total 21 medical directors (58%). Eleven medical directors were educated for the medical director course of the Korean council of emergency medical services physicians. The accuracy of the assessment of the medical directors was 50% in the assessment of electrocardiogram using an automated external defibrillator (AED) in cardiac arrest. Pulse check, respiration check, AED monitoring and the reason of interruption for CPR were lower than 60% for withholding or interruption of CPR. The lowest accurate assessment of medical directors was the appropriate treatment for trauma, with 36.5% in severe trauma. @*Conclusion@#Lower accuracy in some assessments of the medical directors for indirect medical oversight on prehospital care was identified. Education and quality control are needed for medical directors to provide high-quality indirect medical oversight.

A survey on the perception of emergency medical services (EMS) providers and medical directors toward EMS provider’s field skill proficiency

Objective@#This study aimed to investigate the perception of emergency medical service (EMS) providers and medical directors toward the field skill proficiency of EMS providers. We further examined differences in perception according to the certification and hospital career of individuals. @*Methods@#This survey was conducted enrolling all active EMS providers in Busan, Ulsan, and Gyeongnam, as well as emergency physicians who participated in direct medical direction. Pre-developed questionnaires were sent as text messages to individual EMS providers and emergency physicians using an internet-based survey tool (Google Forms).Questionnaires were composed of 25 items in 7 categories: “airway management”, “ventilatory support”, “circulatory support”, “field assessment and management of trauma patients”, “field assessment and management of patients with chest pain”, “field assessment and management of patients with neurologic symptoms”, and “other items”. The response was based on a five-point Likert scale, where 0 score indicated no experience at all. @*Results@#The questionnaire was distributed to 1,781 EMS providers and 52 medical directors; of these, 1,314 (73.7%) EMS providers and 34 (65.3%) medical directors completed the survey. EMS providers rated themselves as above average (3 points) for most of the questions. However, the majority responded that they had no experience or low proficiency in endotracheal intubation and prehospital delivery (median 2; interquartile range [IQR], 0-3). Conversely, medical directors assessed the EMS provider’s proficiency as above average in use of I-gel, recognition of hypoglycemia, field management of trauma patients, use of oropharyngeal and nasopharyngeal airway, use of laryngeal mask airway, and optimal oxygen supply (median, 4; IQR, 3-4), but responded with low scores for most other questions. Based on the EMS provider certification, nurses scored themselves more proficient than level-1 emergency medical technicians (EMTs) for intravenous access (P<0.001), whereas level-1 EMTs recognized themselves more proficient than nurses for endotracheal intubation (P<0.001), use of Magill forceps (P=0.004), and pediatric cardiopulmonary resuscitation (P<0.001). @*Conclusion@#This study recognized the discrepancies in the perception of EMS provider’s field skill proficiency, as perceived by EMS providers and medical directors, and between level-1 EMTs and nurses. We propose that regional EMS authorities need to make persistent efforts to narrow these perception gaps through effective educational programs for EMS providers and medical directors.