An atlas of cancer-associated T cells The tumor microenvironment contains many different kinds of immune cells, the composition, function, and roles of which are unclear. Using single-cell RNA sequencing of T cells in 21 cancer types from more than 300 patients, Zheng et al . identified differences in transcript composition that could be used to catalog different T cell types (see the Perspective by van der Leun and Schumacher). These annotations identified the different roles of specific types of CD4 + and CD8 + T cells among the different tumor types. Some of these clusters revealed evidence for two developmental paths for T cells, one of which shows a trajectory toward the “exhausted” T cell state, knowledge of which may be useful in developing future cancer immunotherapies. —LMZ

PurposeThe role of FDG PET in the evaluation of patients with sepsis of unknown origin remains unclear. We sought to assess the value of FDG PET/CT in patients with sepsis of unknown cause and to define its priority in this group of subjects.MethodsA total of 53 patients with sepsis of unknown origin underwent FDG PET/CT within two weeks of diagnosis. All of the patients were followed up for at least 3 months after discharge to determine the clinical outcomes. The impact of FDG PET/CT was assessed according to the number of cases who had their treatment modified on the basis of the imaging results. Logistic regression analysis was used to identify the independent predictors of positive FDG PET/CT findings.ResultsOf the 53 study patients, 35 (66%) had positive FDG PET/CT findings, and 13 (25%) had their treatment modified on the basis of the imaging results. Logistic regression analysis identified normal serum aspartate aminotransferase (odds ratio [OR]  = 6.134; 95% confidence interval [CI]  = 1.443–26.076, P = 0.014) and increased serum alkaline phosphatase levels (OR = 5.813; 95% CI = 1.386–24.376, P = 0.016) at diagnosis as independent predictors of positive FDG PET/CT findings. A scoring system using these two covariates was developed, which defined three distinct priority groups for FDG PET/CT imaging.ConclusionOur findings suggest that FDG PET/CT may be clinically useful for the detection of occult foci of infection in patients with sepsis of unknown origin.

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Histone deacetylase 6 (HDAC6) acts as a regulator of the nuclear factor kappa-B (NF-κB) signaling pathway by deacetylating the non-histone protein myeloid differentiation primary response 88 (MyD88) at lysine residues, which is an adapter protein for the Toll-like receptor (TLR) and interleukin (IL)-1β receptor. Over-activated immune responses, induced by infiltrated immune cells, excessively trigger the NF-κB signaling pathway in other effector cells and contribute to the development of rheumatoid arthritis (RA). It has also been reported that HDAC6 can promote the activation of the NF-κB signaling pathway. In the present study, we showed that HDAC6 protein level was increased in the synovium tissues of adjuvant-induced arthritis rats. In addition, hydrogen sulfide (H2S) donor S-propargyl-cysteine (SPRC) can inhibit HDAC6 expression and alleviate inflammatory response in vivo. In vitro study revealed that HDAC6 overexpression activated the NF-κB signaling pathway by deacetylating MyD88. Meanwhile, sodium hydrosulfide (NaHS) or HDAC6 inhibitor tubastatin A (tubA) suppressed the pro-inflammatory function of HDAC6. Furthermore, the reduced expression of HDAC6 appeared to result from transcriptional inhibition by S-sulfhydrating specificity protein 1 (Sp1), which is a transcription factor of HDAC6. Our results demonstrate that Sp1 can regulate HDAC6 expression, and S-sulfhydration of Sp1 by antioxidant molecular H2S ameliorates RA progression via the HDAC6/MyD88/NF-κB signaling pathway.

A higher teicoplanin MIC value (≥2.0 mg/L) may predict the treatment failure among patients with teicoplanin-treated MRSA pneumonia.