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The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well‐established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes. [ABSTRACT FROM AUTHOR]

Activation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu2‐xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu2‐xSe) as a copper‐carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis‐driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid‐triggered charge‐switching ability. Next step, the exposed Cu2‐xSe is oxidized and releases divalent copper by high‐level oxide. Then, the abundant copper induces more dihydrolipoamide S‐acetyltransferase oligomerization to down‐regulate FDX1 and tricarboxylic acid cycle‐related proteins, which leads to inhibiting aerobic respiration. Cuproptosis‐induced mitochondrial damage further improves thermotherapy by up‐regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu2‐xSe with sequentially triggered copper‐release, efficient cuproptosis, and appropriate photothermal is a self‐enhanced nanoplatform for cuproptosis‐driven enhancement of thermotherapy. [ABSTRACT FROM AUTHOR]

Cancer photo‐immunotherapy (CPIT) as an ideal strategy can rapidly release hostile signals by appropriate dosage of focal laser irradiation to unmask primary tumor immunogenicity and can activate adaptive immunity to control distant metastases. However, many factors, including disordered immunometabolism, poor penetration of photothermal agents and immuno‐regulators, inadequate laser penetration into the deep tumor region, restrict the therapeutic outcomes of CPIT. Here, a second near‐infrared window (NIR‐II) photo‐immunometabolic cancer therapy (PICT) by a programmed raspberry‐structured nanoadjuvant (PRNMT) is presented that can potentiates efficient immunogenic cell death (ICD) in deep tumor tissue and alleviates immunometabolic disorder. The PRNMT is architected through self‐assembly of indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor modified small‐sized CuS nanoparticles (CuS5) and tumor microenvironment (TME) responsive cationized polymeric matrix. The TME can trigger the splitting and surface cationization of PRNMT into small cationized CuS5 that feature high transcytosis potential and TME immunometabolic regulation. Upon NIR‐II irradiation, CuS5 induce homogeneous ICD and release immunometabolic regulator in deep tumor tissues, which ameliorates IDO‐1 mediated immunometabolic disorder and further suppresses regulatory T cells infiltration. PRNMT mediated PICT effectively delays the primary murine mammary carcinoma 4T1 tumor growth and inhibits the lethal pulmonary metastasis in combination with programmed cell death protein 1 (PD1) blockade. [ABSTRACT FROM AUTHOR]

Under static condition, the pool size of peripheral invariant natural killer T (iNKT) cells is determined by their homeostatic proliferation, survival and thymic input. However, the underlying mechanism is not fully understood. In the present study, we found that the percentage and number of iNKT cells were significantly reduced in the spleen, but not in the thymus of mice with deletion of polybromo‐1 (Pbrm1) compared to wild type (WT) mice. Pbrm1 deletion did not affect iNKT cell proliferation and survival, instead significantly impaired their development from stage 1 to stage 2. Importantly, loss of Pbrm1 led to a dysfunction of RORγt expression and iNKT17 cell differentiation, but not iNKT1 and iNKT2 proportion. Collectively, our study reveals a novel mechanism of Pbrm1 controlling the peripheral size of iNKT cells through regulating their development and differentiation. [ABSTRACT FROM AUTHOR]

Early T‐cell development from CD4− CD8− double‐negative (DN) stage to CD4+ CD8+ double‐positive (DP) stage in the thymus is regulated through multiple steps involving a batch of sequentially expressed factors. Our preliminary data and a recent report showed that AT‐rich interaction domain 1A (Arid1a) is required for the transition from DN to DP stages, but the mechanism is not fully understood. In this study, we consolidated that conditional deletion of Arid1a in T‐cell lineage intrinsically caused developmental blocks from DN3 to DN4 stages, as well as from DN4 to DP stages using both in vivo adoptive T‐cell transfer model and in vitro culture system. The expression of intracellular TCRβ is significantly decreased in Arid1a‐deficient DN4 cells compared with WT cells. OT1 transgenic TCR can rescue the defect in the transition from DN3 to DN4 stages, but not from DN to DP stages. Furthermore, we observed a comparable or stronger proliferation capacity accompanied by a significant increase in cell death in Arid1a−/− DP cells compared with that in WT controls. RNA‐Seq analysis shows a significant enrichment of apoptotic pathway within differentially expressed genes between Arid1a−/− and WT DP cells, including the upregulation of Bim, Casp3 and Trp53 and the downregulation of Rorc, Bcl‐XL and Mcl1. Therefore, our study reveals a novel mechanism that Arid1a controls early T‐cell development by maintaining intracellular TCRβ expression‐mediated β‐selection and activating parallel cell survival pathways. [ABSTRACT FROM AUTHOR]

Under steady‐state conditions, the pool size of peripheral CD8+ T cells is maintained through turnover and survival. Beyond TCR and IL‐7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8+ T cell proportion in spleens but not in thymi of mice with T cell‐specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild‐type (WT) and Med1‐deficient CD8+ T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1‐deficient CD8+ T cells compared with WT counterparts. Finally, Med1‐deficient CD8+ T cells exhibited a decreased expression of interleukin‐7 receptor α (IL‐7Rα), down‐regulation of phosphorylated‐STAT5 (pSTAT5) and Bim up‐regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8+ T cells through IL‐7Rα/STAT5 pathway‐mediated cell survival. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in females. The presence of cancer stem cells ( CSCs) is the main cause of local and distant tumour recurrence and is associated with poor outcome in breast cancer. However, the molecular mechanisms underlying the maintenance of CSCs remain largely unknown. This study demonstrates that prostate tumour overexpressed-1 ( PTOV1) enhances the CSC population and augments the tumourigenicity of breast cancer cells both in vitro and in vivo. Moreover, PTOV1 suppresses transcription of Dickkopf-1 ( DKK1) by recruiting histone deacetylases and subsequently reducing DKK1 promoter histone acetylation, followed by activation of Wnt/β-catenin signalling. Restoration of DKK1 expression in PTOV1-overexpressing cells counteracts the effects of PTOV1 on Wnt/β-catenin activation and the CSC population. Collectively, these results suggest that PTOV1 positively regulates the Wnt/β-catenin signalling pathway and enhances tumourigenicity in breast cancer; this novel mechanism may represent a therapeutic target for breast cancer. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]