Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number.

NK cells are cytotoxic lymphocytes displaying strong antimetastatic activity. Mouse models and in vitro studies suggest a prominent role of the mechanistic target of rapamycin (mTOR) kinase in the control of NK cell homeostasis and antitumor functions. However, mTOR inhibitors are used as chemotherapies in several cancer settings. The impact of such treatments on patients' NK cells is unknown. We thus performed immunophenotyping of circulating NK cells from metastatic breast cancer patients treated with the mTOR inhibitor everolimus over a three-month period. Everolimus treatment resulted in inhibition of mTORC1 activity in peripheral NK cells, whereas mTORC2 activity was preserved. NK cell homeostasis was profoundly altered with a contraction of the NK cell pool and an overall decrease in their maturation. Phenotype and function of the remaining NK cell population was less affected. This is, to our knowledge, the first in vivo characterization of the role of mTOR in human NK cells.

PALLIA-10, a screening tool to identify patients needing palliative care referral in comprehensive cancer centers: A prospective multicentric study (PREPA-10).

PURPOSE: The identification and referral of patients in need of palliative care should be improved. The French society for palliative support and care recommended to use the PALLIA-10 questionnaire and its score greater than 3 to refer patients to palliative care. We explored the use of the PALLIA-10 questionnaire and its related score in a population of advanced cancer patients. METHODS: This prospective multicentric study is to be conducted in authorized French comprehensive cancer centers on hospitalized patients on a given day. We aimed to use the PALLIA-10 score to determine the proportion of palliative patients with a score >3. Main secondary endpoints were to determine the proportion of patients already managed by palliative care teams at the study date or referred to palliative care in six following months, the prevalence of patients with a score greater than 5, and the overall survival using the predefined thresholds of 3 and 5. RESULTS: In 2015, eighteen French cancer centers enrolled 840 patients, including 687 (82%) palliative patients. 479 (69.5%) patients had a score >3, 230 (33.5%) had a score >5, 216 (31.4%) patients were already followed-up by a palliative care team, 152 patients were finally referred to PC in the six subsequent months. The PALLIA-10 score appeared as a reliable predictive (adjusted ORRef≤3 : 1.9 [1.17-3.16] and 3.59 [2.18-5.91]) and prognostic (adjusted HRRef≤3  = 1.58 [95%CI 1.20-2.08] and 2.18 [95%CI 1.63-2.92]) factor for patients scored 4-5 and >5, respectively. CONCLUSION: The PALLIA-10 questionnaire is an easy-to-use tool to refer cancer inpatients to palliative care in current practice. However a score greater than 5 using the PALLIA-10 questionnaire would be more appropriate for advanced cancer patients hospitalized in comprehensive cancer center.

Tonal cues modulate line bisection performance: preliminary evidence for a new rehabilitation prospect?

The effect of the presentation of two different auditory pitches (high and low) on manual line-bisection performance was studied to investigate the relationship between space and magnitude representations underlying motor acts. Participants were asked to mark the midpoint of a given line with a pen while they were listening a pitch via headphones. In healthy participants, the effect of the presentation order (blocked or alternative way) of auditory stimuli was tested (Experiment 1). The results showed no biasing effect of pitch in blocked-order presentation, whereas the alternative presentation modulated the line-bisection. Lower pitch produced leftward or downward bisection biases whereas higher pitch produced rightward or upward biases, suggesting that visuomotor processing can be spatially modulated by irrelevant auditory cues. In Experiment 2, the effect of such alternative stimulations in line bisection in right brain damaged patients with a unilateral neglect and without a neglect was tested. Similar biasing effects caused by auditory cues were observed although the white noise presentation also affected the patient's performance. Additionally, the effect of pitch difference was larger for the neglect patient than for the no-neglect patient as well as for healthy participants. The neglect patient's bisection performance gradually improved during the experiment and was maintained even after 1 week. It is therefore, concluded that auditory cues, characterized by both the pitch difference and the dynamic alternation, influence spatial representations. The larger biasing effect seen in the neglect patient compared to the no-neglect patient and healthy participants suggests that auditory cues could modulate the direction of the attentional bias that is characteristic of neglect patients. Thus, the alternative presentation of auditory cues could be used as rehabilitation for neglect patients. The space-pitch associations are discussed in terms of a generalized magnitude system.