Metal sulfide nanomaterials have emerged as promising photothermal agents for cancer therapy owing to their strong near-infrared absorption, favorable biocompatibility, and tunable surface chemistry. However, insufficient tumor accumulation and limited immunological activation remain major obstacles restricting their therapeutic efficacy in solid tumors. Herein, we report a macrophage-assisted delivery strategy based on hyaluronic acid-engineered copper sulfide nanoparticles (HA@CuS NPs) for enhanced photothermal-immunotherapy against osteosarcoma. In this system, adoptively transferred RAW264.7 macrophages were intravenously administered to increase macrophage enrichment within the osteosarcoma microenvironment, while HA@CuS NPs were rationally designed to target both tumor cells and tumor-associated macrophages through HA-mediated cellular recognition.The HA-coated CuS nanoparticles displayed good colloidal stability, efficient near-infrared photothermal conversion, and enhanced cellular uptake by osteosarcoma cells and macrophages. Importantly, macrophages acted as cellular reservoirs for CuS nanoparticles, promoting tumor accumulation and improving intratumoral photothermal distribution. Under 808-nm laser irradiation, the combined macrophage/HA@CuS treatment produced stronger tumor heating and more effective osteosarcoma ablation than HA@CuS nanoparticles alone. Beyond direct photothermal killing, HA@CuS nanoparticles also remodeled the tumor immune microenvironment by promoting M1-like polarization of tumor-associated macrophages, increasing IL-12p40 secretion, reducing IL-10 levels, and enhancing cytotoxic T lymphocyte infiltration. These immune-regulatory effects further amplified the antitumor response induced by photothermal therapy.Collectively, this study demonstrates that HA-engineered copper sulfide nanoparticles can function not only as metal sulfide photothermal agents but also as immunomodulatory nanomaterials. The integration of macrophage-assisted tumor delivery with CuS-based photothermal therapy provides a promising strategy for improving the therapeutic efficacy of metal-based nanomedicine against osteosarcoma.

PURPOSE:Phosphaturic mesenchymal tumor (PMT) is an ultrarare neoplasm responsible for tumor-induced osteomalacia (TIO). Spinal involvement is exceptionally uncommon, and the diagnostic and therapeutic strategies for spinal PMT remain inadequately defined. This report aims to present a case of thoracic vertebral PMT and review the clinical features, diagnostic challenges, and surgical management of spinal PMTs. METHODS:We reported a 60-year-old male patient presenting with recurrent low back pain and persistent hypophosphatemia. Comprehensive imaging, including CT, MRI, and 18F-AlF-NOTA-octreotide PET/CT, was performed. Given the hypervascularity of the lesion, preoperative segmental artery embolization was conducted to reduce the risk of massive intraoperative hemorrhage. En-bloc tumor resection combined with posterior spinal stabilization was subsequently performed. The literature of previously reported spinal PMT cases was also reviewed. RESULTS:Imaging revealed an osteolytic lesion involving the T11 vertebral body and right pedicle with significant contrast enhancement on CT and MRI. 18F-AlF-NOTA-octreotide PET/CT demonstrated intense uptake in the tumor lesion, and histopathology confirmed the diagnosis of classical type PMT. Preoperative embolization effectively reduced intraoperative blood loss, enabling complete tumor resection. Postoperatively, serum phosphorus level normalized within one week, and his symptoms resolved completely. No recurrence was observed during six months of follow-up. CONCLUSION:Spinal PMT, though rare, should be considered in patients with unexplained hypophosphatemia and osteopenia. 18F-AlF-NOTA-octreotide PET/CT is a valuable tool for tumor localization. Preoperative embolization is an effective adjunctive strategy to reduce intraoperative hemorrhage for hypervascular spinal PMTs. Complete surgical resection remains the definitive treatment, offering excellent biochemical and clinical outcomes.

Neoadjuvant chemotherapy has improved survival rates in osteosarcoma patients. However, reliable pretreatment prognostic markers for predicting treatment outcomes remain limited and underexplored. In this multicenter retrospective study, 308 osteosarcoma patients from ZJU hospital (training cohort) and 141 patients from RJ hospital (testing cohort) who underwent neoadjuvant chemotherapy followed by tumor resection were analyzed. Tumor necrosis rates, complete blood count (CBC) parameters, and various clinical features were evaluated. The training cohort was used to develop a predictive model, which was subsequently validated in the testing cohort. Prognostic factors were evaluated using Chi-square, Mann–Whitney U, Cox regression, and log-rank tests. Most tumors (95.5

Osteoarthritis (OA) is an age-related degenerative disease. Oxidative stress (OS) regulates the pathogenesis of OA by affecting mitochondrial function. Mg2+ and citric acid can delay the progression of OA through reducing OS, but integrated therapy. In this study, a mesoporous nanoparticle (PCMg) composed of Mg2+, citric acid (CC), and dopamine was developed as a novel delivery platform. SS31, a positively charged peptide, was adsorbed onto the surface of PCMg through the charge interaction to obtain the new nanoparticle platform (PCMS). SS31 endowed PCMS with good biocompatibility and enabled it to be rapidly endocytosed by chondrocytes and simultaneously localized in mitochondria. In vitro, PCMS effectively reduced the reactive oxygen species (ROS) level and restored mitochondrial dysfunction mediated by tert-butyl hydroperoxide (TBHP) through reducing OS in chondrocytes. In addition, both in vivo and in vitro results demonstrated that PCMS had no malignant effect on chondrocyte viability and proliferation and was degradable. Through the destabilization of the medial meniscus (DMM) OA model, hematoxylin-eosin (HE), safranin, fast green (SO), and toluidine blue (TB) staining indicated that PCMS effectively alleviated the progression of OA. Comprehensive analysis indicated that PCMS treatment was an effective strategy for alleviating the progression of OA.

Objective:This study aims to investigate the feasibility and oncological outcomes of vessel-sparing surgery for soft tissue sarcomas located near the femoral vessels in the thigh. A comparison was made with cases where the tumor was not adjacent to the femoral vessels, focusing on recurrence rates, survival prognosis, and the viability of vessel-sparing surgical techniques. Methods:A retrospective analysis was conducted on 211 cases. After well-differentiated liposarcoma were excluded from further analysis, 148 cases involved tumors not adjacent to the femoral vessels, while 22 cases were located near the vessels. Postoperative functional outcomes, survival rates, and local recurrence were evaluated. Due to the imbalance in case numbers between the two groups, propensity score matching was applied at a 1:1 ratio, after which the two datasets were compared and analyzed. Results:By the last follow-up, 40 had experienced recurrence, 35 patients had died, 15 were surviving with tumors, and 161 were living tumor-free. No statistically significant differences were found between the survival and recurrence-free survival curves for cases with sarcomas adjacent to the femoral vessels compared to those with tumors located elsewhere, both before and after propensity score matching. Tumor grade and size were identified as key factors influencing survival and recurrence outcomes in soft tissue sarcoma of the thigh. Conclusion:For soft tissue sarcoma of the thigh located adjacent to femoral vessels, vessel-sparing surgery involving vascular sheath removal demonstrates favorable outcomes. Tumor size greater than 10 cm and high pathological grade were significant predictors of survival and recurrence risk.

Schematic of a biomimetic nano-NET strategy based on PCPNAs for the treatment of MRSA-related implant-associated infections.

Osteosarcoma (OS) is a highly malignant and aggressive bone tumor associated with early lung metastasis and high mortality. Traditional chemotherapy does not effectively improve the efficacy and survival rate of patients with OS. Thus, it is vital to search for alternative therapies. Pulsatilla saponin D (PSD) is a potent bioactive compound that has been widely employed in cancer therapy due to its diverse bioactivities and minimal adverse effects. However, any effect on OS remains unclear. We found that PSD induced apoptosis of OS cells and investigated the mechanisms thereof. In vitro, PSD dose-dependently induced apoptosis and inhibited the viability of HOS and K7M2 cells. Furthermore, PSD significantly suppressed cell migration and invasion, and caused cell cycle arrest at the G0/G1 phase. Mechanistically, PSD upregulated ATF3 and JUN transcription by controlling JNK expression. Compared to cells treated with PSD alone, cells pre-treated with SP600125 (a JNK inhibitor), or in which ATF3 had been knocked down ATF3 with siRNA, did not exhibit PSD-mediated cell apoptosis. In a murine OS model, PSD exhibited a powerful anti-cancer effect and an excellent safety profile. Our data imply that PSD could effectively prevent OS occurrence and progression.

Objective:Myxofibrosarcoma (MFS) is a rare malignant fibrogenic soft tissue tumor with high propensity for recurrence. This study retrospectively analyzed the surgical treatment outcomes of patients with myxofibrosarcoma (MFS) at a single center to evaluate the impact of recurrence on survival prognosis. Methods:Clinical data from 80 patients who underwent surgical treatment for MFS between January 2015 and January 2023 were reviewed retrospectively. Postoperative follow-up was conducted to assess recurrence and overall survival. Kaplan-Meier survival analysis was used to estimate overall survival (OS) and compare survival curves. Patients were stratified into recurrence and recurrence-free groups based on recurrence status. Oncological prognosis, prognostic factors influencing survival and recurrence, and the association between recurrence and survival prognosis were examined. Results:Over a median follow-up period of 40.6 months, recurrence was observed in 38 patients (47.5%), including 16 patients with multiple recurrences. A total of 17 patients (21.3%) died, and the 5-year OS rate was 70.1%. Independent prognostic factors for OS included age, tumor size, and chemotherapy. The presence of a tumor adjacent to a major vessel or nerve, as well as involvement of the upper extremity, were identified as independent risk factors for recurrence. No statistically significant differences in survival prognosis were observed between patients with and without recurrence. Additionally, survival outcomes did not differ significantly between patients with a single recurrence and those with multiple recurrences. Conclusion:MFS exhibits a high recurrence rate, with multiple recurrences frequently occurring within three years postoperatively. However, both single and multiple recurrences, when managed with aggressive surgical intervention, may not had an adverse effect on overall survival. For tumors located near major vessels or nerves, achieving complete surgical resection and maintaining vigilant postoperative surveillance are essential to mitigate the risk of recurrence.

BackgroundThis study aimed to evaluate surgical resection techniques for primary malignant tumors of the distal radius and to examine the reconstruction strategies employed for resulting large bone defects.MethodsA retrospective analysis was conducted on 11 cases involving the resection and reconstruction of primary malignant tumors in the distal radius. Complete medical records and follow-up data from December 2013 to December 2022 were reviewed. Oncological outcomes were assessed, with specific focus on the extent of tumor invasion, surgical resection techniques, and reconstruction strategies.ResultsThe follow-up period ranged from 5 to 118 months, with a mean duration of 41.6 months. At the final follow-up, local recurrence was observed in three patients, six died due to disease progression, and five were alive. For tumors confined to the distal radius, resection of the distal radius follow by joint-preserving reconstruction using either autologous fibular grafts or 3D-printed prostheses. For tumors involving the distal radius, proximal carpal bones, and/or distal ulna, wrist arthrodesis are chose using either autologous fibular grafts or ipsilateral ulnar transposition with arthrodesis For tumors involving more than half of the distal radius, reconstruction strategies include ulnar-only fixation or wrist arthrodesis with ipsilateral ulnar transposition.ConclusionsPrimary malignant tumors of the distal radius are rare and associated with a poor prognosis. Selection of resection and reconstruction techniques is primarily influenced by the extent of tumor invasion, with joint-preserving strategies feasible in selected cases and arthrodesis required for more extensive bone involvement.

BACKGROUND T cell receptor (TCR) signaling pathway is closely related to tumor progress and immunotherapy. This study aimed to explore the clinical significance, prognosis, immune infiltration and chemotherapy sensitivity of TCR in osteosarcoma (OS). MATERIAL AND METHODS OS data were obtained from TARGET and GEO database. TCR signaling pathway-related genes (TCRGs) were extracted from Molecular Signatures Database. Unsupervised non-negative matrix factorization clustering analysis was used to identify OS molecular subtypes. Differential expressed TCRGs between molecular subtypes were screened with univariate Cox regression, LASSO regression and multivariate Cox regression. Subsequently, an OS-associated prognostic model was constructed and validated. Nomogram was established and verified. Immune landscape analysis including immune infiltration analysis, ESTIMATE algorithm and immune checkpoints expression levels of molecular subtypes and different risk groups were analyzed. Finally, chemotherapy sensitivity and potential therapeutic agents between different risk groups was identified. RESULTS Two TCRGs related subclusters were identified. Two hundred and seventy-two Differential expressed TCRGs were screened between two subclusters. A robust prognostic model were constructed. High and low risk groups were stratified. Low risk group showed higher ESTIMATE, immune and stromal scores, while high risk group exhibited higher tumor purity and the lower expression levels of immune checkpoints. A nomogram comprising metastasis and risk score was successfully built. The sensitivity to chemotherapy agents were different across high and low risk groups. CONCLUSIONS Our study proposed TCR related molecular subtypes and provided a prognostic model for OS. Our findings may bring a new insight into the immunotherapy for OS patients.

Osteosarcoma (OS) is considered a sex steroid hormone-dependent bone tumor. The development and progression of OS are regulated by 17β-estradiol (E2). However, the detailed mechanisms of E2-modulated OS progression remained to be elucidated. Here, we found that E2-activated mammalian target of rapamycin (mTOR) signaling promoted N6-methyladenosine (m6A) modification through regulating WTAP. Inhibition of mTOR complex 1 (mTORC1) reversed E2-activated WTAP expression. Meanwhile, inhibition of mTORC1 suppressed OS cell proliferation and migration. Deficiency of TSC2 activated mTORC1 signaling and enhanced OS cell proliferation and migration, while abrogated by Rapamycin. Interestingly, mTOMC1 promoted mRNA stability of ubiquitin-specific protease 7 (USP7) through m6A modification. Loss of USP7 suppressed the proliferation, migration, and ASC specks, while promoted apoptosis of OS cells. USP7 interacted with NLRP3 and deubiquitinated NLRP3 through K48-ubiquitination. USP7 was upregulated and positive correlation with NLRP3 in OS patients with high level of E2. Loss of USP7 suppressed the progression of OS via inhibiting NLRP3 inflammasome signaling pathway. Our results demonstrated that E2-activtated mTORC1 promoted USP7 stability, which promoted OS cell proliferation and migration via upregulating NLRP3 expression and enhancing NLRP3 inflammasome signaling pathway. These results discover a novel mechanism of E2 regulating OS progression and provide a promising therapeutic target for OS progression.

The objective of this study is to investigate the impact of fludarabine, a signal transducer and activator of transcription-1 (STAT1) inhibitor, on the radiosensitivity of B-cell lymphoma (BCL) and to explore the underlying mechanisms. Radiotherapy is one of the primary treatments for BCL, and STAT1 plays a critical role in the transcription of cell proliferation-related genes, which are associated with radiotherapy and ferroptosis. This study aims to determine whether fludarabine can enhance the radiosensitivity of BCL and to elucidate the molecular pathways involved. Various in vitro methodologies, including CCK-8 assays, clonogenic formation assays, immunohistochemistry, immunofluorescence, flow cytometry, qRT-PCR, and Western blot analyses, were employed in B-cell lymphoma cell models to thoroughly investigate the effects of fludarabine on radiosensitivity. Subsequently, the obtained results were further validated through in vivo animal models and by examining human diffuse large B-cell lymphoma (DLBCL) cancer samples. Our findings demonstrate that the combination of fludarabine and irradiation synergistically inhibits cell viability and colony formation, while inducing apoptosis and ferroptosis in B-cell lymphoma cell lines Raji and Su-DHL-10. Moreover, fludarabine was found to enhance the ferroptosis induced by radiation, thereby synergistically impeding the growth of BCL. In vivo experiments confirmed these findings, revealing that the intraperitoneal injection of fludarabine significantly enhanced the inhibitory effects of radiation on Raji cell xenograft models, leading to an increased percentage of ferroptosis compared to models without fludarabine. Additionally, the administration of liproxstatin-1, a ferroptosis inhibitor, attenuated the inhibition of xenograft growth caused by the combination of fludarabine and irradiation. Furthermore, our analysis of clinical data revealed that increased co-expression of STAT1 and GPX4 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. These results highlight the potential of fludarabine to enhance radiosensitivity and ferroptosis induction as a promising therapeutic strategy for BCL. Our results demonstrated that fludarabine promoted radiation-induced BCL death through the ferroptosis pathway. We have identified a previously unrecognized mechanism in the fludarabine and radiation combination, indicating that it is necessary to conduct prospective clinical trials to verify this new treatment regimen in BCL. (c) 2024 by Radiation Research Society

OBJECTIVE:In this study, we examined the reason and prognosis of unplanned excision on synovial sarcoma. METHODS:We retrospectively analyzed 54 patients diagnosed with synovial sarcoma between March 2013 and February 2021, including 26 cases of unplanned excision surgery. Patients were divided into two groups based on whether they underwent unplanned excision. Then, factors such as gender, age, tumor size, tumor location, American Joint Committee on Cancer (AJCC) staging, unplanned excision, time of onset, duration of disease, radiotherapy, chemotherapy, amputation, local recurrence factors, and death were statistically evaluated. RESULTS:The results of a multivariate analysis revealed that the AJCC staging is an independent factor for patient prognosis. When patients were divided into two groups, those who had undergone unplanned excision and those who had not, statistical analysis revealed that there was no difference of survival between two groups, but tumor size and AJCC staging had statistical difference. To further explore the influences of unplanned excision, we performed propensity score analysis with 1:1 matching using the nearest neighbor matching method to balance the covariates between the two groups. There was no difference of survival between two groups after propensity score matching. CONCLUSION:Unplanned excision is commonly performed in synovial sarcoma and do not impact the prognosis after extensive resection.

Our previous report has identified a lncRNA SATB2-AS1, which was significantly up-regulated in osteosarcoma tissue and promotes the proliferation of osteosarcoma cells in vitro. However, the mechanisms of SATB2-AS1 regulating the growth and metastasis of osteosarcoma cells in vivo and its role in the prognosis of osteosarcoma patients are still unclear. In this study, the transcriptome sequencing data of 87 patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and 7 patients from our clinical center (GZFPH) was used to evaluate the importance of SATB2-AS1 and SATB2 on the prognosis. The effect of SATB2-AS1 on the growth and metastasis of osteosarcoma cells in vivo was verified by a mouse tumor model. The potential mechanisms of SATB2-AS1 regulating SATB2 were further explored by dual-luciferase reporter gene assay, RNA pull-down assay, and bioinformatics analysis. The results suggested that increased co-expression of SATB2-AS1 and SATB2 was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), and was a biomarker for risk stratification in patients with osteosarcoma. Mechanistically, SATB2-AS1 promotes tumor growth and lung metastasis by regulating SATB2 in vivo. SATB2-AS1 directly binds to POU3F1 for mediating SATB2 expression in MNNG/HOS cells. In addition, SATB2-AS1 and SATB2 might be potential immunomodulators for negatively affecting immune cell infiltration by the IL-17 signaling pathway. In summary, SATB2-AS1 promoted tumor cell growth and lung metastasis by activating SATB2, thereby associated with poor prognosis in patients with osteosarcoma, which indicated that SATB2-AS1 and SATB2 might be novel biomarkers for risk stratification and promising therapeutic targets for osteosarcoma.

There is growing evidence that programmed death ligand-1 (PD-L1) has exciting therapeutic efficacy in hematological malignancy and partial solid tumors. However, many patients still face failure with the treatment of immune checkpoint blockade because of PD-L1 expression regulation during transcription and post-transcription processes, including N6-methyladenosine (m6A). Similar to the epigenetic regulation in DNA and histones, recent research has revealed the essential regulation of m6A modification in RNA nuclear export, metabolism and translation. Recent studies have shown that m6A-induced PD-L1 expression emerges as one of the main reasons for the immunological alteration in this process and contributes to the failure of T cell-induced anti-tumor immunity. The results of preclinical studies demonstrate the potential of m6A-targeted therapy in combination with immune checkpoint blockade. The comprehensive expression of m6A-related genes also provided the possibility to indicate the prognosis and to optimize the treatment for patients of various cancer types. In this review, we focus on the m6A modification in PD-L1 mRNA as well as the regulation of PD-L1 expression in cancer cells and summarize its clinical value in anti-PD-L1 cancer immune therapy.

AIMS:Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation.METHODS:A total of 122 patients who underwent reconstruction following resection of periacetabular tumour between January 2011 and January 2020 were studied. The risk factors for dislocation were investigated with univariate and multivariate logistic regression analysis on patient-specific, resection-specific, and reconstruction-specific variables.RESULTS:The dislocation rate was 13.9% (n = 17). The hip COR was found to be significantly shifted anteriorly and inferiorly in most patients in the dislocation group compared with the non-dislocation group. Three independent risk factors were found to be related to dislocation: resection of gluteus medius (odds ratio (OR) 3.68 (95% confidence interval (CI) 1.24 to 19.70); p = 0.039), vertical shift of COR > 18 mm (OR 24.8 (95% CI 6.23 to 128.00); p = 0.001), and sagittal shift of COR > 20 mm (OR 6.22 (95% CI 1.33 to 32.2); p = 0.026).CONCLUSION:Among the 17 patients who dislocated, 70.3% (n = 12) were anterior dislocations. Three independent risk factors were identified, suggesting the importance of proper restoration of the COR and the role of the gluteus medius in maintaining hip joint stability.Cite this article: Bone Joint J 2022;104-B(10):1180-1188.

ABSTRACT The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation of immune tolerance mechanisms in the osteosarcoma microenvironment and a new therapeutic strategy. Clearance of apoptotic cells by phagocytes, a process termed “efferocytosis,” is ubiquitous in tumors and mediates the suppression of innate immune inflammatory response. Considering the massive infiltrated macrophages in osteosarcoma, efferocytosis probably serves as a potential target, but is rarely studied in osteosarcoma. Here, we verified M2 polarization and PD-L1 expression of macrophages following efferocytosis. Pharmacological inhibition and genetic knockdown were used to explore the underlying pathway. Moreover, tumor progression and immune landscape were evaluated following inhibition of efferocytosis in osteosarcoma model. Our study indicated that efferocytosis promoted PD-L1 expression and M2 polarization of macrophages. Ëfferocytosis was mediated by MerTK receptor in osteosarcoma and regulated the phenotypes of macrophages through the p38/STAT3 pathway. By establishing the murine osteosarcoma model, we emphasized that inhibition of MerTK suppressed tumor growth and enhanced the T cell cytotoxic function by increasing the infiltration of CD8+ T cells and decreasing their exhaustion. Our findings demonstrate that MerTK-mediated efferocytosis promotes osteosarcoma progression by enhancing M2 polarization of macrophages and PD-L1-induced immune tolerance, which were regulated through the p38/STAT3 pathway.

As the main immune checkpoint, PD-L1-PD-1 interaction plays a critical role in the dysregulation of effector T cells, which contributes to the failure of Chimeric Antigen Receptor T-cell (CAR-T) and other immunotherapies. Presently, most research focuses on the extracellular function of PD-L1. Membrane PD-L1 can interact with its receptor PD-1 and decrease T cell-induced cancer immunity. However, the function of PD-L1 in cancer cells is still unclear. Recent studies have shown the separated clinical significance of PD-L1 expression in various cancer types, showing the complexity of PD-L1 in cancer cell regulation. As a novel regulatory pathway, the nuclear translocation of PD-L1 in cancer cells receives more attention. Results of these preclinical studies demonstrated that nuclear PD-L1 has an essential role in cancer development and other immune checkpoint molecules transcription. Herein, we summarized the mechanisms involved in PD-L1 nuclear transportation and identify the key regulatory factors in this process. Furthermore, we also summarize the function of nuclear PD-L1 in cancer immunity. These findings suggested the novel PD-L1 regulation in cancer development, which showed that nuclear PD-L1 is a potential therapeutic target in future cancer therapy.

The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation of immune tolerance mechanisms in the osteosarcoma microenvironment and a new therapeutic strategy. Clearance of apoptotic cells by phagocytes, a process termed "efferocytosis," is ubiquitous in tumors and mediates the suppression of innate immune inflammatory response. Considering the massive infiltrated macrophages in osteosarcoma, efferocytosis probably serves as a potential target, but is rarely studied in osteosarcoma. Here, we verified M2 polarization and PD-L1 expression of macrophages following efferocytosis. Pharmacological inhibition and genetic knockdown were used to explore the underlying pathway. Moreover, tumor progression and immune landscape were evaluated following inhibition of efferocytosis in osteosarcoma model. Our study indicated that efferocytosis promoted PD-L1 expression and M2 polarization of macrophages. Ëfferocytosis was mediated by MerTK receptor in osteosarcoma and regulated the phenotypes of macrophages through the p38/STAT3 pathway. By establishing the murine osteosarcoma model, we emphasized that inhibition of MerTK suppressed tumor growth and enhanced the T cell cytotoxic function by increasing the infiltration of CD8+ T cells and decreasing their exhaustion. Our findings demonstrate that MerTK-mediated efferocytosis promotes osteosarcoma progression by enhancing M2 polarization of macrophages and PD-L1-induced immune tolerance, which were regulated through the p38/STAT3 pathway.