MR1-Restricted T Cells in Cancer Immunotherapy
CANCERS
Authors: Flores-Villanueva, Pedro; Sobhani, Navid; Wang, Xu; Li, Yong
Abstract
Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) alpha-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells' TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.
Infant hydrocephalus in sub-Saharan Africa: Impact of perioperative care in the Zanzibar archipelago
NEUROCIRUGIA
Authors: Moreno Oliveras, Luis; Llacer Ortega, Jose Luis; Leidinger, Andreas; Ali Haji, Mohamed; Chisbert Genoves, Maria Pilar; Piquer Belloch, Jose
Abstract
Introduction: Child hydrocephalus in low- and middle-income countries represents one of the most sensitive ethical and health problems facing international health development. The most optimistic estimates indicate that 200,000 newborns annually will develop hydrocephalus or be born with a neural tube defect in East, Central and South Africa (ECSA). It is estimated that less than 10% of these children will be operated by ventriculoperitoneal shunts, and in general in poor quality conditions or with a very high complication rate. Objective: To describe the general characteristics, epidemiology and demographic data of childhood hydrocephalus of patients treated at the NED Institute in the Zanzibar archipelago, and assess the clinical details and medium-term results of the impact of the set-up nursing care. Material and methods: This is a descriptive and analytical observational study of a retrospective nature, in patients diagnosed and treated with childhood hydrocephalus, in the period from September 2016 to September 2018. With the implementation of a series of perioperative nursing protocols in these patients, the results obtained were described and analyzed. Results: A total of 96 patients were treated for childhood hydrocephalus. 51% (n = 49) of these patients were male, with a mean age of 9.25 months. All the mothers of the patients were monitored during pregnancy, but only 8% were treated with folic acid during pregnancy. 81% of children were born through vaginal delivery or uncomplicated spontaneous delivery. Regarding the etiology, 27.1% of treated hydrocephalus was associated with an infectious cause and 35.4% with an unknown cause. 67 ventriculoperitoneal shunt surgery and 15 endoscopic ventriculostomies were performed. The complication rate was 23.17%. Conclusions: The results of this research indicate that childhood hydrocephalus in Zanzibar has etiology, evolution and complications that are similar to or less than those described to date in East Africa. Implementing a series of perioperative protocols and standardized nursing care positively influences the results obtained. Currently, the Mnazi Mmoja Surgical NED Institute is one of the few centers in East Africa with an exhaustive record of healthcare activity and is the first health center that offers further training to nurses. (C) 2020 Sociedad Espanola de Neurocirugia. Published by Elsevier Espana, S.L.U. All rights reserved.