Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4⁺ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3⁺ T cells with high proportion of TIGIT⁺ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

Background: Sarcomas are a heterogeneous group of rare but deadly malignant tumors. The aim of this study was to comprehensively describe the incidence and mortality of sarcomas in Shanghai during 2002–2014. Method: Data were from Shanghai Cancer Registry. All new cases diagnosed with sarcomas and all death records where the cause of death listed as sarcomas were included. The characteristics of sarcomas incidence and mortality were analyzed. Age-standardized rates (ASRs) were adjusted by the world standard population. The trends were assessed by Joinpoint analysis. Results: A total of 9,440 incident cases were identified. The ASR was 3.4/10⁵ for all sarcomas combined. Incidence of sarcomas overall was similar in females (3.5/10⁵) as in males (3.4/10⁵). Except for sarcomas “Not Otherwise Specified” (NOS), the most common histological subtype was gastrointestinal stromal sarcoma (GISS) (14.8%), which was followed by fibrosarcoma (7.2%), lipoblastoma (6.7%), leiomyosarcomas (6.5%), and osteosarcoma (5.3%). Among those incident cases, 87.9% were located in soft tissue sarcomas (STS) and 12.1% in bone and joint (bone sarcomas). The ASRs for STS and bone sarcomas were 2.8/10⁵ and 0.6/10⁵, respectively. Incidence rates for all STS combined rose exponentially with age, while bone sarcomas had the highest incidence at age 0–19. There were 4,279 deaths during 2002–2014 with the ASR of 1.3/10⁵. Age-adjusted mortality due to sarcomas was slightly higher in males (1.5/10⁵) than females (1.2/10⁵). Except for sarcomas NOS, leiomyosarcomas was the most common subtype, comprising 9.9% of deaths due to sarcomas, followed by lipoblastoma (6.4%) and osteosarcoma (6.3%). The ASRs of mortality for STS and bone sarcomas were 1.0/10⁵ and 0.2/10⁵, respectively. For both males and females, the age-standardized incidence for STS and bone sarcomas did not change meaningfully over the study period. In contrast, age-standardized STS mortality in females increased by 2.3% per year (95% CI: 0.3, 4.4%), but was unchanged in males. No meaningful trends in bone sarcomas mortality were observed for either males or females. Conclusion: This population-based study was the first report of epidemiology of sarcomas in Shanghai according to anatomic site and histologic type. The diversity and rarity of sarcomas suggested more detailed data are warranted.