Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses.

BACKGROUND: The physiological and immunological characteristics of the tumor microenvironment (TME) have a profound impact on the effectiveness of immunotherapy. The present study aimed to define the TME subtype of osteosarcoma according to the signatures representing the global TME of the tumor, as well as create a new prognostic assessment tool to monitor the prognosis, TME activity and immunotherapy response of patients with osteosarcoma. METHODS: The enrichment scores of 29 functional gene expression signatures in osteosarcoma samples were calculated by single sample gene set enrichment analysis (ssGSEA). TME classification of osteosarcoma was performed and a prognostic assessment tool was created based on 29 ssGSEA scores to comprehensively correlate them with TME components, immunotherapy efficacy and prognosis of osteosarcoma. RESULTS: Three TME subtypes were generated that differed in survival, TME activity and immunotherapeutic response. Four differentially expressed genes between TME subtypes were involved in the development of prognostic assessment tools. The established prognosis assessment tool had strong performance in both training and verification cohorts, could be effectively applied to the survival prediction of samples of different ages, genders and transfer states, and could well distinguish the TME status of different samples. CONCLUSIONS: The present study describes three different TME phenotypes in osteosarcoma, provides a risk stratification tool for osteosarcoma prognosis and TME status assessment, and provides additional information for clinical decision-making of immunotherapy.

Engineering Ga-doped mesoporous bioactive glass-integrated PEEK implants for immunomodulatory and enhanced osseointegration effects.

With the increasing aging population, the demand for orthopedic implants is also growing. Polyether ether ketone (PEEK) is considered a promising material for orthopedic implants due to its excellent biocompatibility. However, the lack of bioactivity and excessive immune response post-implantation often impair bone integration. Therefore, it is urgent to bio-functionalize PEEK-based implants to promote bone integration. This study employs a simple, economical, and feasible method to coat Ga-ion doped bioactive glass nanoparticles (Ga-MBGs) onto sulfonated PEEK surfaces, constructing a multifunctional PEEK-based orthopedic implant. The resulting bio-functionalized PEEK implants promote macrophage M2 phenotype polarization, thus fostering an anti-inflammatory immune microenvironment. Moreover, the direct osteogenic effect of Ga ions and the immuno-osteogenic effect through promoting macrophage M2 polarization enhance osteogenic differentiation potential in vitro and bone integration in vivo. A sequence of in vivo and in vitro experiments substantiates the essential and intricate function of this innovative orthopedic implants. in regulating normal bone immunity and metabolism. Overall, the application of Ga-MBGs provides a simple, economical, and effective method for developing multifunctional orthopedic implants. This surface bio-functionalized PEEK implant, capable of modulating immunity and bone metabolism, holds significant clinical application potential as an orthopedic implant.