Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiotherapies, chemotherapies, and small-molecule inhibitors exert immune-mediated anti-tumor responses. In this review, we discuss the mechanisms of immunogenic cell death and immunogenic modulation and their relevance in the anti-tumor activity of radiotherapies, chemotherapies, and small-molecule inhibitors. Our aim is to feature the immunological aspects of conventional and targeted cancer therapies and highlight how these therapies may be compatible with emerging immunotherapy approaches.

Microbiota of the Oropharynx and Endoscope Compared to the Esophagus.

The role of the microflora in the development of esophageal disease is still largely unknown and is being investigated in more detail. Our goal was to determine how the microbiota levels of endoscope and uvular swabs compared to the levels of tissue biopsies along various points of the esophagus. 17 patients with Barrett's esophagus agreed to participate in the study. Biopsies of esophageal mucosa were taken from the (1) proximal esophagus, (2) mid-esophagus, (3) distal esophagus, and (4) Barrett's esophagus. Swabs were also taken from the uvula and the endoscope. Throughout the esophagus, 17 bacterial genera were detected from the samples. The microflora pattern obtained from the uvula and endoscopic swabs did not correlate well with mucosal biopsies along any aspect of the esophagus. There were statistically significant differences in the levels and proportions of bacteria found when comparing the uvula swab to the esophageal biopsies and when comparing the endoscope swab to the esophageal biopsies. Obtaining a simple swab of the uvula or endoscope itself appears to be a poor substitute for tissue biopsy of esophageal mucosa when evaluating microflora patterns. When performing microflora studies of the esophagus, mucosal biopsies should be used for analysis.

Altering Physical Activity Influences Insulin Responses to Glucose Ingestion in Healthy Adults.

This study determined if varying physical activity (PA) the day prior to an oral glucose tolerance test (OGTT) differentially influenced postprandial glucose and insulin kinetics. Fifteen healthy, young adults participated in three OGTT trials the morning after performing 50% (LOW), 100% (HABITUAL), or 150% (HIGH) of their habitual PA (determined by 7-day pedometry). Trials were randomized and separated by at least 1-wk. For each OGTT trial, blood glucose and insulin were measured after an overnight fast and at 30-min intervals for 2 h following ingestion of the glucose beverage. Between-trial differences were analyzed using a general linear model with repeated measures. Subjects successfully achieved the desired percentage of habitual steps prior to each trial: LOW: 51±5%, HABITUAL: 99±6%, and HIGH: 149±9%. Fasting blood glucose and glucose total area under the curve (AUC) did not differ between trials. Serum insulin AUC was lower (p<0.05) following the HIGH (34,158±8,786 pmol·min·L-1) compared to the LOW (40,738±9,276 pmol·min·L-1) trial. No differences were observed when the LOW and HIGH trials were compared to HABITUAL. These data suggest that varying the PA level (from 50 to 150% of habitual PA) the day prior to an OGTT influences the insulin (but not blood glucose) response to an OGTT.