Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK.

Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. However, the utility of γδ T cells as APCs to induce CD8+ T cell-mediated antitumor immune response, as well as the mechanism by which they perform APC functions, remains unexplored. In this study, we found that activated Vγ9Vδ2 T cells were capable of inducing robust CD8+ T cell responses in osteosarcoma cells. Activated γδ T cells also effectively suppressed osteosarcoma growth by priming CD8+ T cells in xenograft animal models. Mechanistically, we further revealed that activated γδ T cells exhibited increased HSP90 production, which fed back to upregulate MyD88, followed by JNK activation and a subsequent improvement in CCL5 secretion, leading to enhanced CD8+ T cell cross-priming. Thus, our study suggests that Vγ9Vδ2 T cells represent a promising alternative APC for the development of γδ T cell-based tumor immunotherapy.

Survey on Exact kNN Queries over High-Dimensional Data Space.

k nearest neighbours (kNN) queries are fundamental in many applications, ranging from data mining, recommendation system and Internet of Things, to Industry 4.0 framework applications. In mining, specifically, it can be used for the classification of human activities, iterative closest point registration and pattern recognition and has also been helpful for intrusion detection systems and fault detection. Due to the importance of kNN queries, many algorithms have been proposed in the literature, for both static and dynamic data. In this paper, we focus on exact kNN queries and present a comprehensive survey of exact kNN queries. In particular, we study two fundamental types of exact kNN queries: the kNN Search queries and the kNN Join queries. Our survey focuses on exact approaches over high-dimensional data space, which covers 20 kNN Search methods and 9 kNN Join methods. To the best of our knowledge, this is the first work of a comprehensive survey of exact kNN queries over high-dimensional datasets. We specifically categorise the algorithms based on indexing strategies, data and space partitioning strategies, clustering techniques and the computing paradigm. We provide useful insights for the evolution of approaches based on the various categorisation factors, as well as the possibility of further expansion. Lastly, we discuss some open challenges and future research directions.

Survey of Collision Avoidance Systems for Underground Mines: Sensing Protocols.

With the growing number of unintentional interactions occurring in underground mines, Collision Avoidance System (CAS) establishment and maintenance has become an urgent need for mining industries to enhance their risk profile and improve construction safety. Usually, most collision accidents can be divided into three different categories in line with the involved participants and infrastructure condition. The accidents pose a great risk of financial cost to mining companies and even cause casualties. In detail, this paper presents an intensive study survey of positioning techniques, including ranging algorithms, to accommodate the demands of various proximity sensors and improve the capability of situational awareness. Then, we exploit the importance of the communication system, prevalent low-power wide-area technologies and related communication protocols. The effectiveness of communication systems decides and facilitates the success of the final integrated system that can be used to fundamentally address the problem of collision avoidance. For the purpose of collaboration between communication systems and other executive departments, a series of systematic comparisons of pertinent technologies and algorithms is given near the end, followed by a brief discussion on the best choice among these options. In the proposed solution, the overall end-to-end delay can be minimised to a few nanoseconds and the localisation accuracy can achieve centimetre level when operating in the range of 100 m.

Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment.

Blockade of immune-checkpoint programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 can enhance effector T-cell responses. However, the lack of response in many patients to checkpoint-inhibitor therapies emphasizes the need for combination immunotherapies to pursue maximal antitumor efficacy. We have previously demonstrated that antagonism of C-X-C chemokine receptor type 4 (CXCR4) by plerixafor (AMD3100) can decrease regulatory T (Treg)-cell intratumoral infiltration. Therefore, a combination of these 2 therapies might increase antitumor effects. Here, we evaluated the antitumor efficacy of AMD3100 and anti-PD-1 (αPD-1) antibody alone or in combination in an immunocompetent syngeneic mouse model of ovarian cancer. We found that AMD3100, a highly specific CXCR4 antagonist, directly down-regulated the expression of both C-X-C motif chemokine 12 (CXCL12) and CXCR4 in vitro and in vivo in tumor cells. AMD3100 and αPD-1 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice when given as monotherapy. Combination of these 2 agents significantly enhanced antitumor effects compared with single-agent administration. Benefits of tumor control and animal survival were associated with immunomodulation mediated by these 2 agents, which were characterized by increased effector T-cell infiltration, increased effector T-cell function, and increased memory T cells in tumor microenvironment. Intratumoral Treg cells were decreased, and conversion of Treg cells into T helper cells was increased by AMD3100 treatment. Intratumoral myeloid-derived suppressor cells were decreased by the combined treatment, which was associated with decreased IL-10 and IL-6 in the ascites. Also, the combination therapy decreased suppressive leukocytes and facilitated M2-to-M1 macrophage polarization in the tumor. These results suggest that AMD3100 could be used to target the CXCR4-CXCL12 axis to inhibit tumor growth and prevent multifaceted immunosuppression alone or in combination with αPD-1 in ovarian cancer, which could be clinically relevant to patients with this disease.-Zeng, Y., Li, B., Liang, Y., Reeves, P. M., Qu, X., Ran, C., Liu, Q., Callahan, M. V., Sluder, A. E., Gelfand, J. A., Chen, H., Poznansky, M. C. Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment.

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine.

Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC (migDC) populations, specifically increasing and activating the Lang+ and CD11b-Lang- subsets in skin, and that the Ab responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave NIR laser adjuvant showed limited effects on the migDC subsets. Our vaccination study demonstrated that the efficacy of the CW NIR laser is significantly better than that of the pulsed wave laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migDCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migDC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by an NIR laser-adjuvanted vaccine.

An Emergency Seamless Positioning Technique Based on ad hoc UWB Networking Using Robust EKF.

In this paper, a new emergency positioning technique is proposed based on ad hoc GNSS/UWB (Global Navigation Satellite System/Ultra-Wideband) network. The main innovations of the program are reflected in two aspects. First of all, a unified coordinate frame for indoor and outdoor environments is constructed dynamically with GNSS/UWB integration. In the outdoor environments, the high accuracy positioning can be achieved with GNSS/UWB equipment. The high-accuracy indoor coordinate is obtained by measuring the range observations between adjacent network nodes and outdoor GNSS/UWB nodes, and the range information of the UWB network is transmitted to the cloud server center. A network adjustment algorithm is proposed to improve the positioning accuracy of the UWB network. Secondly, a UWB indoor location algorithm based on robust EKF (Extended Kalman Filter) is proposed. By analyzing the transfer characteristics of gross error in EKF model, a new robust EKF model is established. The model is constructed based on the statistical characteristics of redundant observation components and prediction residual. The robust equivalent gain matrix is constructed, and the robust positioning solution of UWB is obtained with iteration. The global test is carried out first to further improve the real-time operation efficiency. Finally, a field indoor and outdoor seamless positioning experiment was carried out to verify the effectiveness of the proposed algorithm. The results show that the positioning accuracy of UWB emergency network nodes (anchors) can reach 0.35 m. Based on the network, the positioning accuracy of the tag can reach 0.38 m by applying the improved robust EKF positioning algorithm, which is improved by 20.83% and 73.43% compared with standard EKF and least square method, respectively.

Bone combined cement grafting in giant cell tumor around the knee reduces mechanical failure.

OBJECTIVES: The aims of our study are (1) to explore the risk factors of mechanical failure (MF), (2) to figure out an index to evaluate this risk, and (3) to select an optimal reconstruction strategy to reduce this risk. METHODS: We retrospectively reviewed 104 patients from Dec. 2008 to Mar. 2016, undergone extensive knee curettages in our institution. Radiographs and post-operative interviews were used to classified cases of MF. Relative factors (age, tumor location, the invaded area, etc.) were also collected and analyzed by SPSS software. RESULTS: Thick subchondral bony layer (p = 0.006) and combined grafting of the cement and bone (p = 0.006) had lower risk of mechanical failure. Mechanical failure appeared to happen in the femur (p = 0.012) more easily. The ROC curve (AUC = 0.722) reveals that less post-operative bony layer (≤ 3.3 mm) is more likely to cause mechanical failure. The Kaplan-Meier survival curve showing increased survival in those patients after a combination grafting surgery (HR, 3.799; p = 0.006). CONCLUSION: Based on our study results, combined grafting of the cement and bone reduced the risk of mechanical failure in the knee due to the thin subchondral bone layer (SCB), especially in the femur.

Epigenetic alterations in osteosarcoma: promising targets.

Cancer is being reinterpreted due to recent discoveries related to epigenetic regulation during development, and the importance of epigenetic mechanisms in initiation and progression of cancer has been further highlighted by the recent explosion in medical information. Osteosarcoma is highly genetically unstable, and current therapeutic regimens are subject to chemoresistance and tumor relapse. Understanding the epigenetic mechanisms in the pathogenesis of osteosarcoma will provide novel avenues for cancer therapy. In this review, we examine the epigenetic alterations in gene expression in osteosarcoma, and discuss the utilization of epigenetic regulation therapy in treatment against osteosarcoma.

A Vondrak low pass filter for IMU sensor initial alignment on a disturbed base.

The initial alignment of the Inertial Measurement Unit (IMU) is an important process of INS to determine the coordinate transformation matrix which is used in the integration of Global Positioning Systems (GPS) with Inertial Navigation Systems (INS). In this paper a novel alignment method for a disturbed base, such as a vehicle disturbed by wind outdoors, implemented with the aid of a Vondrak low pass filter, is proposed. The basic principle of initial alignment including coarse alignment and fine alignment is introduced first. The spectral analysis is processed to compare the differences between the characteristic error of INS force observation on a stationary base and on disturbed bases. In order to reduce the high frequency noise in the force observation more accurately and more easily, a Vondrak low pass filter is constructed based on the spectral analysis result. The genetic algorithms method is introduced to choose the smoothing factor in the Vondrak filter and the corresponding objective condition is built. The architecture of the proposed alignment method with the Vondrak low pass filter is shown. Furthermore, simulated experiments and actual experiments were performed to validate the new algorithm. The results indicate that, compared with the conventional alignment method, the Vondrak filter could eliminate the high frequency noise in the force observation and the proposed alignment method could improve the attitude accuracy. At the same time, only one parameter needs to be set, which makes the proposed method easier to implement than other low-pass filter methods.

Scalable and Effective Temporal Graph Representation Learning With Hyperbolic Geometry.

Real-life graphs often exhibit intricate dynamics that evolve continuously over time. To effectively represent continuous-time dynamic graphs (CTDGs), various temporal graph neural networks (TGNNs) have been developed to model their dynamics and topological structures in Euclidean space. Despite their notable achievements, the performance of Euclidean-based TGNNs is limited and bounded by the representation capabilities of Euclidean geometry, particularly for complex graphs with hierarchical and power-law structures. This is because Euclidean space does not have enough room (its volume grows polynomially with respect to radius) to learn hierarchical structures that expand exponentially. As a result, this leads to high-distortion embeddings and suboptimal temporal graph representations. To break the limitations and enhance the representation capabilities of TGNNs, in this article, we propose a scalable and effective TGNN with hyperbolic geometries for CTDG representation (called STGNh ). It captures evolving behaviors and stores hierarchical structures simultaneously by integrating a memory-based module and a structure-based module into a unified framework, which can scale to billion-scale graphs. Concretely, a simple hyperbolic update gate (HuG) is designed as the memory-based module to store temporal dynamics efficiently; for the structure-based module, we propose an effective hyperbolic temporal Transformer (HyT) model to capture complex graph structures and generate up-to-date node embeddings. Extensive experimental results on a variety of medium-scale and billion-scale graphs demonstrate the superiority of the proposed STGNh for CTDG representation, as it significantly outperforms baselines in various downstream tasks.

Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study.

BACKGROUND: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. METHODS: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. RESULTS: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10-2, 1.7 × 10-2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10-4, 9.5 × 10-4, respectively). CONCLUSION: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted.

Efficacy and Safety of Fruquintinib-Based Treatment in Patients with Refractory Bone and Soft Tissue Sarcoma after Developing Resistance to Several TKIs: A Multicenter Retrospective Study.

OBJECTIVE: Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second-line therapy in refractory sarcoma, prolonging progression-free survival (PFS) but with short-lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. METHODS: We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib-based treatment from November 2021 to August 2023. The primary endpoint was the progression-free survival rate at 4 months (4m-PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan-Meier method. A log-rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS-related prognostic factors. RESULTS: We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow-up time of 6.8 (interquartile range [IQR], 4.6-9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m-PFSR was 58.4% (95% confidence interval [CI], 49.6%-67.1%). The median PFS and OS were 4.4 (95% CI, 3.9-5.0) months and 11.4 (95% CI, 10.3-12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10-2.93; p = 0.020). Eighty-eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). CONCLUSIONS: Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.

First-Line Anlotinib Treatment for Soft Tissue Sarcoma in Chemotherapy-Ineligible Patients: An Open-label, Single-arm, Phase 2 Clinical Trial.

PURPOSE: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma (LA/M STS) is chemotherapy based on anthracyclines, but patient tolerance of chemotherapy is limited. The present trial (NCT03792542) investigated the use of anlotinib as first-line treatment for patients with advanced STS, in particular liposarcoma (LPS). PATIENTS AND METHODS: Eligible patients were previously untreated, pathologically confirmed, unresectable LA/M STS cases. Anlotinib was given orally at a dose of 12 mg once daily from day 1 to day 14 every 3 weeks until disease progression or intolerable adverse events (AEs) occurred. The primary endpoint was progression-free survival (PFS) and the secondary endpoints overall survival (OS), the objective response rate and the disease control rate (DCR). The safety profile was also evaluated. RESULTS: Forty patients were enrolled from April 2019 to Jun 2022 and are included in the intention-to-treat analysis. The median PFS was 6.83 months [95% confidence interval (CI): 4.17-8.71] and the median OS 27.40 months (95% CI: 16.43-not evaluable); 1 patient reached partial response and 26 attained stable disease, with a DCR of 67.5% (27/40). Median PFS and OS times for LPS patients were 8.71 and 16.23 months, respectively. Ten (25.0%) patients had treatment-related AEs ≥ grade 3, with in particular a higher incidence of hypertension (15.0%) and proteinuria (7.5%). CONCLUSIONS: The findings suggest a potential benefit in employing front-line anlotinib to treat patients with STS, who are not eligible for cytotoxic chemotherapy. Of note, the clinical outcomes for the LPS subgroup of patients were encouraging.

Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.

Bone is one of the most common sites of tumor metastases. During the last step of bone metastasis, cancer cells colonize and disrupt the bone matrix, which is maintained mainly by osteocytes, the most abundant cells in the bone microenvironment. However, the role of osteocytes in bone metastasis is still unclear. Here, we demonstrated that osteocytes transfer mitochondria to metastatic cancer cells and trigger the cGAS/STING-mediated antitumor response. Blocking the transfer of mitochondria by specifically knocking out mitochondrial Rho GTPase 1 (Rhot1) or mitochondrial mitofusin 2 (Mfn2) in osteocytes impaired tumor immunogenicity and consequently resulted in the progression of metastatic cancer toward the bone matrix. These findings reveal the protective role of osteocytes against cancer metastasis by transferring mitochondria to cancer cells and potentially offer a valuable therapeutic strategy for preventing bone metastasis.

An improved algorithm to generate a Wi-Fi fingerprint database for indoor positioning.

The major problem of Wi-Fi fingerprint-based positioning technology is the signal strength fingerprint database creation and maintenance. The significant temporal variation of received signal strength (RSS) is the main factor responsible for the positioning error. A probabilistic approach can be used, but the RSS distribution is required. The Gaussian distribution or an empirically-derived distribution (histogram) is typically used. However, these distributions are either not always correct or require a large amount of data for each reference point. Double peaks of the RSS distribution have been observed in experiments at some reference points. In this paper a new algorithm based on an improved double-peak Gaussian distribution is proposed. Kurtosis testing is used to decide if this new distribution, or the normal Gaussian distribution, should be applied. Test results show that the proposed algorithm can significantly improve the positioning accuracy, as well as reduce the workload of the off-line data training phase.

Learning Accurate Label-Specific Features From Partially Multilabeled Data.

Feature selection is an effective dimensionality reduction technique, which can speed up an algorithm and improve model performance such as predictive accuracy and result comprehensibility. The study of selecting label-specific features for each class label has attracted considerable attention since each class label might be determined by some inherent characteristics, where precise label information is required to guide label-specific feature selection. However, obtaining noise-free labels is quite difficult and impractical. In reality, each instance is often annotated by a candidate label set that comprises multiple ground-truth labels and other false-positive labels, termed partial multilabel (PML) learning scenario. Here, false-positive labels concealed in a candidate label set might induce the selection of false label-specific features while masking the intrinsic label correlations, which misleads the selection of relevant features and compromises the selection performance. To address this issue, a novel two-stage partial multilabel feature selection (PMLFS) approach is proposed, which elicits credible labels to guide accurate label-specific feature selection. First, the label confidence matrix is learned to help elicit ground-truth labels from the candidate label set via the label structure reconstruction strategy, each element of which indicates how likely a class label is ground truth. After that, based on distilled credible labels, a joint selection model, including label-specific feature learner and common feature learner, is designed to learn accurate label-specific features to each class label and common features for all class labels. Besides, label correlations are fused into the features selection process to facilitate the generation of an optimal feature subset. Extensive experimental results clearly validate the superiority of the proposed approach.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Cancer cells reprogram to metastatic state through the acquisition of platelet mitochondria.

Metastasis is the major cause of cancer deaths, and cancer cells evolve to adapt to various tumor microenvironments, which hinders the treatment of tumor metastasis. Platelets play critical roles in tumor development, especially during metastasis. Here, we elucidate the role of platelet mitochondria in tumor metastasis. Cancer cells are reprogrammed to a metastatic state through the acquisition of platelet mitochondria via the PINK1/Parkin-Mfn2 pathway. Furthermore, platelet mitochondria regulate the GSH/GSSG ratio and reactive oxygen species (ROS) in cancer cells to promote lung metastasis of osteosarcoma. Impairing platelet mitochondrial function has proven to be an efficient approach to impair metastasis, providing a direction for osteosarcoma therapy. Our findings demonstrate mitochondrial transfer between platelets and cancer cells and suggest a role for platelet mitochondria in tumor metastasis.