CD1c self-reactive T cells recognize a novel class of self-lipids that are accumulated on leukemia cells.

Background:In selected patients with refractory out-of-hospital cardiac arrest, extracorporeal cardiopulmonary resuscitation represents a promising approach when conventional cardiopulmonary resuscitation fails to achieve return of spontaneous circulation. This systematic review and meta-analysis aimed to compare extracorporeal cardiopulmonary resuscitation to conventional cardiopulmonary resuscitation. Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials up to November 28, 2021, for randomized trials and observational studies reporting propensity score-matched data and comparing adults with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation with those treated with conventional cardiopulmonary resuscitation. The primary outcome was survival with favorable neurological outcome at the longest follow-up available. Secondary outcomes were survival at the longest follow-up available and survival at hospital discharge/30 days. Results: We included six studies, two randomized and four propensity scorematched studies. Patients treated with extracorporeal cardiopulmonary resuscitation had higher rates of survival with favorable neurological outcome (81/584 [14%] vs. 46/593 [7.8%]; OR = 2.11; 95% CI, 1.41-3.15; p < 0.001, number needed to treat 16) and of survival (131/584 [22%] vs. 102/593 [17%]; OR = 1.40; 95% CI, 1.05-1.87; p = 0.02) at the longest follow-up available compared with conventional cardiopulmonary resuscitation. Survival at hospital discharge/30 days was similar between the two groups (142/584 [24%] vs. 122/593 [21%]; OR = 1.26; 95% CI, 0.95-1.66; p = 0.10). Conclusions: Evidence from randomized trials and propensity score-matched studies suggests increased survival and favorable neurological outcome in patients with refractory out-of-hospital cardiac arrest treated with extracorporeal

Adoptive immunotherapy with T cells engineered with tumor-specific T cell receptors (TCRs) holds promise for cancer treatment. However, suppressive cues generated in the tumor microenvironment (TME) can hinder the efficacy of these therapies, prompting the search for strategies to overcome these detrimental conditions and improve cellular therapeutic approaches. CD1d-restricted invariant natural killer T (iNKT) cells actively participate in tumor immunosurveillance by restricting suppressive myeloid populations in the TME. Here, we showed that harnessing iNKT cells with a second TCR specific for a tumor-associated peptide generated bispecific effectors for CD1d- and major histocompatibility complex (MHC)–restricted antigens in vitro. Upon in vivo transfer, TCR-engineered iNKT (TCR-iNKT) cells showed the highest efficacy in restraining the progression of multiple tumors that expressed the cognate antigen compared with nontransduced iNKT cells or CD8 + T cells engineered with the same TCR. TCR-iNKT cells achieved robust cancer control by simultaneously modulating intratumoral suppressive myeloid populations and killing malignant cells. This dual antitumor function was further enhanced when the iNKT cell agonist α-galactosyl ceramide (α-GalCer) was administered as a therapeutic booster through a platform that ensured controlled delivery at the tumor site, named multistage vector (MSV). These preclinical results support the combination of tumor-redirected TCR-iNKT cells and local α-GalCer boosting as a potential therapy for patients with cancer.

T cell responses are generally regarded as specific for protein-derived peptide antigens. This is based on the molecular paradigm dictated by the T cell receptor (TCR) recognition of peptide-major histocompatibility complexs, which provides the molecular bases of the specificity and restriction of the T cell responses. An increasing number of findings in the last 20 years have challenged this paradigm, by showing the existence of T cells specific for lipid antigens presented by CD1 molecules. CD1-restricted T cells have been proven to be frequent components of the immune system and to recognize exogenous lipids, derived from pathogenic bacteria, as well as cell-endogenous self-lipids. This represents a young and exciting area of research in immunology with intriguing biological bases and a potential direct impact on human health.