BackgroundBullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients.ObjectiveWe evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth.Methods and resultsA multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment.ConclusionDupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.

RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m5C) has attracted increasing attention in recent years due to the improvement in RNA m5C site detection methods. By influencing transcription, transportation and translation, m5C modification of mRNA, tRNA, rRNA, lncRNA and other RNAs has been proven to affect gene expression and metabolism and is associated with a wide range of diseases, including malignant cancers. RNA m5C modifications also substantially impact the tumor microenvironment (TME) by targeting different groups of immune cells, including B cells, T cells, macrophages, granulocytes, NK cells, dendritic cells and mast cells. Alterations in immune cell expression, infiltration and activation are highly linked to tumor malignancy and patient prognosis. This review provides a novel and holistic examination of m5C-mediated cancer development by examining the exact mechanisms underlying the oncogenicity of m5C RNA modification and summarizing the biological effects of m5C RNA modification on tumor cells as well as immune cells. Understanding methylation-related tumorigenesis can provide useful insights for the diagnosis as well as the treatment of cancer.

IntroductionMycoplasma pneumoniae (MP) is a major pathogen of community-acquired pneumonia in children. However, the specific pathogenesis of the progression of Mycoplasma pneumoniae pneumonia (MPP) is unclear. We aimed to reveal the landscape of microbiota and the host immune response in MPP.MethodsThis self-controlled study analyzed the microbiome and transcriptome of bronchoalveolar lavage fluid (BALF) from the severe side (SD) and opposite side (OD) of 41 children with MPP from January to December 2021 and revealed the differences of the peripheral blood neutrophil function among children with mild MPP, severe MPP, and healthy children through transcriptome sequencing.ResultsThe MP load or the pulmonary microbiota had no significant difference between the SD group and OD group, and the deterioration of MPP was related to the immune response, especially the intrinsic immune response.DiscussionThe immune response plays a role in MPP, which may inform treatment strategies for MPP.

ObjectiveWe report the efficacy and safety of serplulimab, a novel humanized anti–programmed death-1 antibody, plus nanoparticle albumin-bound (nab)-paclitaxel in previously treated patients with programmed death ligand-1 (PD-L1)–positive advanced cervical cancer.MethodsPatients diagnosed with PD-L1–positive (combined positive score ≥1) cervical cancer were enrolled in this single-arm, open-label, phase II study. They were given serplulimab 4.5 mg/kg for up to 2 years (35 dosing cycles) plus nab-paclitaxel 260 mg/m2 for up to six cycles once every 3 weeks. Primary endpoints were safety and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST version 1.1. Secondary endpoints included ORR assessed by the investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsBetween December 2019 and June 2020, 52 patients were screened and 21 were enrolled. IRRC-assessed ORR was 57.1% (95% confidence interval [CI] 34.0–78.2%); 3 (14.3%) patients achieved complete response and 9 (42.9%) partial response. The median DOR was not reached (NR) (95% CI 4.1–NR). IRRC-assessed median PFS was 5.7 months (95% CI 3.0–NR), and median OS was 15.5 months (95% CI 10.5–NR). Investigator-assessed ORR was 47.6% (95% CI 25.7–70.2%). Seventeen (81.0%) patients experienced grade ≥3 treatment-emergent adverse events. Grade ≥3 adverse drug reactions were reported in 7 (33.3%) patients. Immune-related adverse events occurred in 12 (57.1%) patients.ConclusionsIn previously treated patients with PD-L1–positive advanced cervical cancer, serplulimab plus nab-paclitaxel provided durable clinical activity and a manageable safety profile.Clinical trial registrationClinicalTrials.gov, identifier NCT04150575.

Chimeric antigen receptor (CAR)-T cell therapy is an innovative treatment for CD19-expressing lymphomas. CAR-T cells are primarily manufactured via lentivirus transfection or transposon electroporation. While anti-tumor efficacy comparisons between the two methods have been conducted, there is a current dearth of studies investigating the phenotypes and transcriptome alterations induced in T cells by the two distinct manufacturing methods. Here, we established CAR-T signatures using fluorescent imaging, flow cytometry, and RNA-sequencing. A small fraction of CAR-T cells that were produced using the PiggyBac transposon (PB CAR-T cells) exhibited much higher expression of CAR than those produced using a lentivirus (Lenti CAR-T cells). PB and Lenti CAR-T cells contained more cytotoxic T cell subsets than control T cells, and Lenti CAR-T cells presented a more pronounced memory phenotype. RNA-sequencing further revealed vast disparities between the two CAR-T cell groups, with PB CAR-T cells exhibiting greater upregulation of cytokines, chemokines, and their receptors. Intriguingly, PB CAR-T cells singularly expressed IL-9 and fewer cytokine release syndrome-associated cytokines when activated by target cells. In addition, PB CAR-T cells exerted faster in vitro cytotoxicity against CD19-expressing K562 cells but similar in vivo anti-tumor efficacy with Lenti CAR-T. Taken together, these data provide insights into the phenotypic alterations induced by lentiviral transfection or transposon electroporation and will attract more attention to the clinical influence of different manufacturing procedures.

Multicellular organisms live in environments containing diverse nutrients and a wide variety of microbial communities. On the one hand, the immune response of organisms can protect from the intrusion of exogenous microorganisms. On the other hand, the dynamic coordination of anabolism and catabolism of organisms is a necessary factor for growth and reproduction. Since the production of an immune response is an energy-intensive process, the activation of immune cells is accompanied by metabolic transformations that enable the rapid production of ATP and new biomolecules. In insects, the coordination of immunity and metabolism is the basis for insects to cope with environmental challenges and ensure normal growth, development and reproduction. During the activation of insect immune tissues by pathogenic microorganisms, not only the utilization of organic resources can be enhanced, but also the activated immune cells can usurp the nutrients of non-immune tissues by generating signals. At the same time, insects also have symbiotic bacteria in their body, which can affect insect physiology through immune-metabolic regulation. This paper reviews the research progress of insect immune-metabolism regulation from the perspective of insect tissues, such as fat body, gut and hemocytes. The effects of microorganisms (pathogenic bacteria/non-pathogenic bacteria) and parasitoids on immune-metabolism were elaborated here, which provide guidance to uncover immunometabolism mechanisms in insects and mammals. This work also provides insights to utilize immune-metabolism for the formulation of pest control strategies.