The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

Enhanced Therapeutic Potential of Liposome-Coated Bushen Jianpi Recipe for Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) poses a major healthcare burden globally. Traditional Chinese medicine formula Bushen Jianpi (BSJP) recipe shows inhibitory effects on HCC but suffers from low bioavailability. This study aims to develop a BSJP-loaded liposome (BSJP@Lip) for targeted HCC treatment. METHODS: BSJP@Lip was prepared using a microfluidic device. Particle characterization included size, morphology, drug loading, encapsulation efficiency, and release kinetics analysis. In vitro cytotoxicity, cellular uptake, apoptosis, and protein expression were evaluated in hepG2, Smmc-7721, and hepa 1-6 hepatic cancer cell lines treated with BSJP@Lip. RESULTS: BSJP@Lip nanoparticles showed a uniform spherical shape with an average size of 50 nm and zeta potential at around -2.24 mV. They significantly inhibited cell viability and induced apoptosis in a dose-dependent manner compared with traditional decoction formulations. Enhanced cellular uptake of BSJP@Lip increased the expression of proinflammatory factors IL-18 and NLRP3. CONCLUSION: BSJP@Lip nanoparticles were found to be efficiently internalized by hepatic cancer cell lines, resulting in a dose-dependent inhibition of cell viability and induction of apoptosis. This effect was accompanied by the upregulation of IL-18 and NLRP3.

Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway.

This study investigated the impact of PM2.5 on promoting EMT in PM2.5-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM2.5. Four groups of male SD rats were formed: control (0 mg/kg.bw), low (1 mg/kg.bw), medium (5 mg/kg.bw), and high-dose (25 mg/kg.bw) PM2.5 groups. Experimental rats were subjected to PM2.5 exposure via intratracheal instillation, given once weekly for 16 weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM2.5 concentrations with/without inhibitors for 24 h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM2.5 damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM2.5 exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM2.5-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM2.5-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM2.5, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM2.5. Our findings suggest PM2.5 mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.

Dual-energy computed tomography for predicting cervical lymph node metastasis in laryngeal squamous cell carcinoma.

Rationale and objectives: We constructed a dual-energy computed tomography (DECT)-based model to assess cervical lymph node metastasis (LNM) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods: We retrospectively analysed 164 patients with LSCC who underwent preoperative DECT from May 2019 to May 2023. The patients were randomly divided into training (n = 115) and validation (n = 49) cohorts. Quantitative DECT parameters of the primary tumours and their clinical characteristics were collected. A logistic regression model was used to determine independent predictors of LNM, and a nomogram was constructed along with a corresponding online model. Model performance was assessed using the area under the curve (AUC) and the calibration curve, and the clinical value was evaluated using decision curve analysis (DCA). Results: In total, 64/164 (39.0 %) patients with LSCC had cervical LNM. Independent predictors of LNM included normalized iodine concentration in the arterial phase (odds ratio [OR]: 8.332, 95 % confidence interval [CI]: 2.813-24.678, P < 0.001), normalized effective atomic number in the arterial phase (OR: 5.518, 95 % CI: 1.095-27.818, P = 0.002), clinical T3-4 stage (OR: 5.684, 95 % CI: 1.701-18.989, P = 0.005), and poor histological grade (OR: 5.011, 95 % CI: 1.003-25.026, P = 0.049). These predictors were incorporated into the DECT-based nomogram and the corresponding online model, showing good calibration and favourable performance (training AUC: 0.910, validation AUC: 0.918). The DCA indicated a significant clinical benefit of the nomogram for estimating LNM. Conclusions: DECT parameters may be useful independent predictors of LNM in patients with LSCC, and a DECT-based nomogram may be helpful in clinical decision-making.

The causal link between nitrogen structure and physiological processes of Ulva prolifera as the causative species of green tides.

Harmful algal blooms (HABs) increase with eutrophication depending on the nutrient structure (availability and ratios), but an unequivocal causal link between these factors is rarely established. Here, we provide support for the causal link between the nitrogen structure and physiological processes of Ulva prolifera as the causative species of Yellow Sea green tides (YSGTs) using in situ and laboratory experiments. The results showed that the components of nitrogen nutrients in seawater exhibited significant spatiotemporal variation. The concentration of NO3--N showed a notable decreasing trend from south to north. Sufficient dissolved inorganic nitrogen (DIN) induced increases in thalli nitrate reductase (NR) and glutamine synthetase (GS) activities. This could accelerate thalli uptake of nitrogen nutrients. The glutamate dehydrogenase (GDH) activity was significantly upregulated with the increasing proportion of dissolved organic nitrogen (DON) in seawater. The change in nitrogen structure regulated the activity of NR during the long-distance floating migration of the YSGTs. And the activity of NR could modulate the nitric oxide (NO) content in the thalli. NO was used as a signal molecule to enhance the antioxidant defense system of thalli. The efficient antioxidant system in the thalli could reduce oxidative stress and effectively maintain high photosynthetic activity. The findings deepen our understanding of the relationship between nitrogen structures and key biological processes in macroalgae. This study also suggest that NO can enhance key biological processes in U. prolifera under varying nitrogen structures.

Construction of circRNA-mediated ceRNA network and immunoassay for investigating pathogenesis of COPD.

Background: The chronic respiratory condition known as chronic obstructive pulmonary disease (COPD) was one of the main causes of death and disability worldwide. This study aimed to explore and elucidate new targets and molecular mechanisms of COPD by constructing competitive endogenous RNA (ceRNA) networks. Methods: GSE38974 and GSE106986 were used to select DEGs in COPD samples and normal samples. Cytoscape software was used to construct and present protein-protein interaction (PPI) network, mRNA-miRNA co-expression network and ceRNA network. The CIBERSORT algorithm and the Lasso model were used to screen the immune infiltrating cells and hub genes associated with COPD, and the correlation between them was analyzed. COPD cell models were constructed in vitro and the expression level of ceRNA network factors mediated by hub gene was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: In this study, 852 differentially expressed genes were screened in the GSE38974 dataset, including 439 upregulated genes and 413 downregulated genes. Gene clustering analysis of PPI network results was performed using the Minimum Common Tumor Data Element (MCODE) in Cytoscape, and seven hub genes were screened using five algorithms in cytoHubba. CCL20 was verified as an important hub gene based on mRNA-miRNA co-expression network, GSE106986 database validation and the analysis of ROC curve results. Finally, we successfully constructed the circDTL-hsa-miR-330-3p-CCL20 network by Cytoscape. Immune infiltration analysis suggested that CCL20 can co-regulate immune cell migration and infiltration through chemokines CCL7 and CXCL3. In vitro experiments, the expression of circDTL and CCL20 was increased, while the expression of hsa-miR-330-3p was decreased in the COPD cell model. Conclusion: By constructing the circDTL-hsa-miR-330-3p-CCL20 network, this study contributes to a better understanding of the molecular mechanism of COPD development, which also provides important clues for the development of new therapeutic strategies and drug targets.

Reversible chemoresistance of pancreatic cancer grown as spheroids.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Bi-phase CT radiomics nomogram for the preoperative prediction of pylorus lymph node metastasis in non-pyloric gastric cancer patients.

BACKGROUND: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown. METHODS: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated. RESULTS: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values. CONCLUSION: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies.

Scalable, Controlled Bimodal Pore-Structured Polymer Coating for Efficient Passive Daytime Radiative Cooling.

Outdoor thermal irritation poses a serious threat to public health, with the frequent occurrence of increasingly intense heat waves. With the global goal of carbon peaking and carbon neutrality, there is an urgent need for a strategy that is efficient and can provide localized outdoor cooling without an intensive energy input. This paper demonstrated a rapidly formable polyurethane-based coating with controlled bimodal spherical micropores. Nano-Al2O3 particles (300 nm) embedded in the polymer were used for targeted enhancement of reflectance at 0.38-0.5 wavelengths. The enhanced film reflected 93% solar irradiance and selectively transmitted 95% thermal radiation (8-13 µm), enabling rapid cooling and the creation of a comfortable thermal microclimate to avoid overheating of 6-11 °C during daytime conditions. The ultrawide material compatibility and excellent adaptive mechanical strength of polyurethane-based coatings are expected to benefit the sustainable development of society in a wide range of fields, from health to economics.

Comparative Genomics Revealing the Genomic Characteristics of Klebsiella variicola Clinical Isolates in China.

Klebsiella variicola is an opportunistic pathogen often misidentified as Klebsiella pneumoniae, leading to misdiagnoses and inappropriate treatment in clinical settings. The genetic and molecular characteristics of clinically isolated K. variicola remain largely unexplored. We aim to fill this knowledge gap by examining the genomic properties of and evolutionary relationships between clinical isolates of K. variicola. The genomic data of 70 K. variicola strains were analyzed using whole-genome sequencing. A phylogenetic tree was generated based on the gene sequences from these K. variicola strains and public databases. Among the K. variicola strains, the drug resistance genes with the highest carrying rates were beta-lactamase and aminoglycoside. Locally isolated strains had a higher detection rate for virulence genes than those in public databases, with yersiniabactin genes being the most prevalent. The K locus types and MLST subtypes of the strains exhibited a dispersed distribution, with O3/O3a being the predominant subtype within the O category. In total, 28 isolates carried both IncFIB(K)_Kpn3 and IncFII_pKP91 replicons. This study underscores the importance of developing more effective diagnostic tools and therapeutic strategies for K. variicola infections. The continued surveillance and monitoring of K. variicola strains is essential for understanding the epidemiology of infections and informing public health strategies.

Construction of "ant-like tentacle" structure for ultra-sensitive detection of low-concentration ammonia through colorimetric fluorescent dual-signal gas-sensitive cotton fabric.

Detection and monitoring of ammonia (NH3) are crucial in various industries, including plant safety management, food freshness testing, and water pollution control. Nevertheless, creating portable, low-cost, highly sensitive, and easily regenerated ppm-level NH3 sensors poses a significant challenge. In this investigation, an innovative "ant-like tentacle" fabrication strategy was proposed, and a colorimetric fluorescent dual-signal gas-sensitive cotton fabric (PAH-fabric) for NH3 detection was successfully prepared by conventional dyeing using suitable molecular-level photoacid (PAH) sensitive units. The visual recognition lower detection limit of the ultra-low is 1.09 ppm-level. PAH-fabric is not only straightforward, convenient, and cost-effective to prepare, but it can also be efficiently regenerated and recycled multiple times (maintaining excellent gas-sensitive performance even after 100 cycles) by strategically leveraging volatile acid fumigation. Detailed molecular reaction mechanisms involved in the NH3 response and PAH-fabric regeneration are elucidated. PAH-fabric, available either as a portable kit or an alarm system, offers a promising approach for ultra-low NH3 detection. The demonstrated "ant-like tentacle" fabrication strategy introduces numerous possibilities for designing and developing sensors with adjustable response thresholds, particularly those requiring high sensitivity.

Bimetal loaded graphitic carbon nitride with synergistic enhanced peroxidase-like activity for colorimetric detection of p-phenylenediamine.

In recent years, great progress has been made on the study of nanozymes with enzyme-like properties. Here, bimetallic Fe and Ni nanoclusters were anchored on the nanosheets of nitrogen-rich layered graphitic carbon nitride by one-step pyrolysis at high temperature (Fe/Ni-CN). The loading content of Fe and Ni on Fe/Ni-CN is as high as 8.0%, and Fe/Ni-CN has a high specific surface area of 121.86 m2 g-1. The Fe/Ni-CN can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and exhibits efficient peroxidase-like activity, leading to a 17.2-fold increase compared to pure graphitic carbon nitride (CN). Similar to the natural horseradish peroxidase (HRP), the Fe/Ni-CN nanozyme follows catalytic kinetics. The Michaelis-Menten constant (Km) value of the Fe/Ni-CN nanozyme for TMB is about 8.3-fold lower than that for HRP, which means that the Fe/Ni-CN nanozyme has better affinity for TMB. In addition, the catalytic mechanism was investigated by combination of free radical quenching experiments and density-functional theory (DFT) calculations. The results show that the high peroxidase-like activity is due to the easy adsorption of H2O2 after bimetal loading, which is conducive to the production of hydroxyl radicals. Based on the extraordinary peroxidase-like activity, the colorimetric detection of p-phenylenediamine (PPD) was constructed with a wide linear range of 0.2-30 µM and a low detection limit of 0.02 µM. The sensor system has been successfully applied to the detection of residual PPD in real dyed hair samples. The results show that the colorimetric method is sensitive, highly selective and accurate. This study provides a new idea for the efficient enhancement of nanozyme activity and effective detection of PPD by a bimetallic synergistic strategy.

Role of land-ocean interactions in stepwise Northern Hemisphere Glaciation.

The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth's surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Novel Biomaterials for Wound Healing and Tissue Regeneration.

Skin is the first defense barrier of the human body, which can resist the invasion of external dust, microorganisms and other pollutants, and ensure that the human body maintains the homeostasis of the internal environment. Once the skin is damaged, the health threat to the human body will increase. Wound repair and the human internal environment are a dynamic process. How to effectively accelerate the healing of wounds without affecting the internal environment of the human body and guarantee that the repaired tissue retains its original function as much as possible has become a research hotspot. With the advancement of technology, researchers have combined new technologies to develop and prepare various types of materials for wound healing. This article will introduce the wound repair materials developed and prepared in recent years from three types: nanofibers, composite hydrogels, and other new materials. The paper aims to provide reference for researchers in related fields to develop and prepare multifunctional materials. This may be helpful to design more ideal materials for clinical application, and then achieve better wound healing and regeneration effects.

Deciphering functional groups of rumen microbiome and their underlying potentially causal relationships in shaping host traits.

Over the years, microbiome research has achieved tremendous advancements driven by culture-independent meta-omics approaches. Despite extensive research, our understanding of the functional roles and causal effects of the microbiome on phenotypes remains limited. In this study, we focused on the rumen metaproteome, combining it with metatranscriptome and metabolome data to accurately identify the active functional distributions of rumen microorganisms and specific functional groups that influence feed efficiency. By integrating host genetics data, we established the potentially causal relationships between microbes-proteins/metabolites-phenotype, and identified specific patterns in which functional groups of rumen microorganisms influence host feed efficiency. We found a causal link between Selenomonas bovis and rumen carbohydrate metabolism, potentially mediated by bacterial chemotaxis and a two-component regulatory system, impacting feed utilization efficiency of dairy cows. Our study on the nutrient utilization functional groups in the rumen of high-feed-efficiency dairy cows, along with the identification of key microbiota functional proteins and their potentially causal relationships, will help move from correlation to causation in rumen microbiome research. This will ultimately enable precise regulation of the rumen microbiota for optimized ruminant production.

Prognostic value of left ventricular structure and strain in chronic kidney disease patients by cardiovascular magnetic resonance imaging: a retrospective study.

Background: Individuals suffering from chronic kidney disease (CKD) frequently face a heightened likelihood of experiencing cardiovascular complications, including heart failure and cardiac mortality. Cardiovascular magnetic resonance feature tracking (CMR-FT) is utilized to assess the micro-contraction function of the myocardium. The objective of this research is to explore the relationship between the left ventricular anatomy, myocardial strain, and the clinical outcomes in patients with CKD. Methods: A total of 77 patients with late-stage CKD were enrolled in this retrospective study. They underwent cardiac magnetic resonance imaging and were followed up, with no history of significant cardiac diseases. The patients were divided into two groups: those with a left ventricular global longitudinal strain (LVGLS) ≥ -15.2% (n = 49) and those with LVGLS < -15.2% (n = 28). The clinical endpoints were defined as hospitalization for heart failure or all-cause mortality. Results: Over an average observation period of 22 ± 9 months, 11 (14%) patients passed away and 30 (39%) were admitted to the hospital for heart failure, with eight encountering both incidents. Those with LVGLS ≥ -15.2% had markedly lower rates of event-free survival concerning heart failure admissions and overall mortality than their counterparts (log-rank P = 0.014). Cox multivariable analysis indicated that reduced LVGLS consistently predicted a higher likelihood of combined outcomes of heart failure admissions and total mortality (HR: 3.40, 95% CI [1.35-8.56], P = 0.009), even when factoring in age, diabetes, left atrial diameter, and left ventricular mass index (LVMI). However, the LVMI showed no significant correlation with the risk of heart failure admissions or overall mortality. Conclusion: Compared to patients with LVGLS < -15.2%, CKD patients with LVGLS ≥ -15.2% have an increased risk of heart failure hospitalization and all-cause mortality. The prognostic role of LVMI in assessing CKD patients among the Asian population requires further investigation.

The biological applications of near-infrared optical nanomaterials in atherosclerosis.

PURPOSE OF REVIEW: Atherosclerosis, a highly pathogenic and lethal disease, is difficult to locate accurately via conventional imaging because of its scattered and deep lesions. However, second near-infrared (NIR-II) nanomaterials show great application potential in the tracing of atherosclerotic plaques due to their excellent penetration and angiographic capabilities. RECENT FINDINGS: With the development of nanotechnology, among many nanomaterials available for the visual diagnosis and treatment of cardiovascular diseases, optical nanomaterials provide strong support for various biomedical applications because of their advantages, such as noninvasive, nondestructive and molecular component imaging. Among optical nanomaterials of different wavelengths, NIR-II-range (900 ~ 1700 nm) nanomaterials have been gradually applied in the visual diagnosis and treatment of atherosclerosis and other vascular diseases because of their deep biological tissue penetration and limited background interference. This review explored in detail the prospects and challenges of the biological imaging and clinical application of NIR-II nanomaterials in treating atherosclerosis.

Predicting prognosis outcomes of primary central nervous system lymphoma with high-dose methotrexate-based chemotherapeutic treatment using lipidomics.

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy which is commonly treated with high-dose methotrexate (HD-MTX)-based chemotherapy. However, the prognosis outcome of HD-MTX-based treatment cannot be accurately predicted using the current prognostic scoring systems, such as the Memorial Sloan-Kettering Cancer Center (MSKCC) score. Methods: We studied 2 cohorts of patients with PCNSL and applied lipidomic analysis to their cerebrospinal fluid (CSF) samples. After removing the batch effects and features engineering, we applied and compared several classic machine-learning models based on lipidomic data of CSF to predict the relapse of PCNSL in patients who were treated with HD-MTX-based chemotherapy. Results: We managed to remove the batch effects and get the optimum features of each model. Finally, we found that Cox regression had the best prediction performance (AUC = 0.711) on prognosis outcomes. Conclusions: We developed a Cox regression model based on lipidomic data, which could effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.