The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here, we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and to impair cytotoxic T-cell homing to the tumor site. Analysis of human osteosarcoma cases further revealed that CXCL12 expression strongly correlated with overall survival. Evaluations on fresh human chemotherapy-free osteosarcoma samples also showed a positive correlation between CXCL12 concentration and the number of intratumoral lymphocytes. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth. These antitumor effects were abrogated by CXCL12-CXCR4 blockade or CD8 T-cell depletion. Collectively, our data show that CXCL12 regulation plays a significant role in both tumor progression and immune response, and targeting CXCL12 is promising for therapeutics against osteosarcoma. Epigenetic regulation of CXCL12 controls metastasis and immune response in osteosarcoma, suggesting epigenetic therapies or therapies targeting CXCL12 have potential for therapeutic intervention in osteosarcoma. .

Purpose : Chondrosarcoma with metastatic disease has a very poor prognosis. However, the prognosis and potential prognostic factors of patients with primary chondrosarcoma of bone and metastasis at presentation have not been documented because of its rarity. Therefore, we examined the prognosis of this special cohort and identify possible prognostic factors. Methods : The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify patients with primary chondrosarcoma of bone and metastatic disease at diagnosis from 2000 to 2013. The prognostic analysis was performed using the Kaplan-Meier method and a Cox proportional hazards regression model. Results : The SEER database contained 264 cases. The overall survival (OS) and cancer-survival specific (CSS) rates of the entire group at 5 years were 28.4% and 31.2%, respectively. The median OS and CSS were 14.0 ± 2.5 and 17.0 ± 2.6 months, respectively. Multivariate analysis revealed that low tumor grade, surgical treatment, tumor size < 10 cm, and first primary tumor were associated with improved OS. Tumor grade, tumor size, and surgery were independent predictors of CSS. Radiation therapy had no effect on either OS or CSS. Conclusion : Among patients with primary chondrosarcoma of bone and metastasis at presentation, low tumor grade, surgical treatment, tumor size < 10 cm, and first primary tumor predict prolonged survival.

Purpose: Older osteosarcoma patients have a very poor prognosis and treatment for them remains a challenge. The outcomes and potential prognostic factors of primary or secondary older osteosarcoma patients are rarely documented. Therefore, we examined the prognosis of the two special cohorts to identify possible prognostic factors, and provide optimal treatment strategy for them.Methods: The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify osteosarcoma patients aged over 40 years from 1973 to 2015. The prognostic analysis was performed using the Kaplan-Meier method and a Cox proportional hazards regression model.Results: In total, 1162 primary older osteosarcoma patients and 444 secondary older osteosarcoma patients were eligible for this study. The OS and CSS rates of the primary older osteosarcoma patients at 5-year were 38.5% and 37.1%, respectively. The 3- and 5-year OS rates of the secondary older osteosarcoma patients were 22.8% and 14.6%, respectively. On multivariate analysis of the primary older osteosarcoma patients, age > 60, male, axial site, high grade, metastasis, tumor size>10 cm, no surgery, and radiation treatment were negatively associated with OS. In terms of CSS, age, gender, decade of diagnosis, tumor site, tumor grade, tumor stage, tumor size, and surgery were independent prognostic factors. A multivariate Cox regression model showed that secondary older osteosarcoma patients of high grade, metastasis, tumor size > 10 cm, no surgery, and no chemotherapy were independent predictors of decreased OS.Conclusions: Surgery in combination with chemotherapy should be recommended for the treatment of the secondary older osteosarcoma patients, while for the primary older osteosarcoma patients, only surgery should be recommended.

No abstract

Reconstruction with a non-vascularized proximal fibular autograft is a reasonable option after en bloc resection of the distal radius for giant cell tumor of bone.