Lu Xie

B7 homolog 3 protein (B7-H3), a member of the B7 checkpoint family, is aberrantly and consistently expressed on the membranes of various human cancer cells and is associated with poor prognosis. Emerging evidence also indicates that soluble B7-H3 (sB7-H3) correlates with adverse outcomes in multiple malignancies. In this study, we measured sB7-H3 levels in peripheral blood using an enzyme-linked immunosorbent assay (ELISA) from 100 newly diagnosed osteosarcoma (OTS) patients, both before and after neoadjuvant chemotherapy, and simultaneously assessed B7-H3 tissue expression via immunohistochemistry (IHC) analysis of surgical specimens. Our analysis showed significant associations between B7-H3 tissue expression and histopathological response to chemotherapy, with the H-score threshold > 75 identifying patients with particularly poor prognosis (p < 0.05). Although no significant correlation was observed between tissue and circulating B7-H3 expression, we found that lower baseline sB7-H3 levels (pre-sB7H3 < 21.2425 ng/mL) predicted poor clinical outcomes. By integrating sB7-H3 levels with established prognostic indicators, including metastatic status and lactate dehydrogenase (LDH) levels, we developed a comprehensive prognostic model that demonstrated strong predictive accuracy for survival outcomes. Notably, pre-sB7-H3 levels were significantly associated with good histological responses (p < 0.05). Longitudinal monitoring during treatment revealed that dynamic changes in sB7-H3 levels positively correlated with disease progression (p < 0.05) and inversely correlated with good histological responses (p < 0.05). These findings highlight serum sB7-H3 as a clinically valuable biomarker in OTS, providing prognostic information both at diagnosis and throughout the course of treatment in a relatively convenient manner.

CD3L1 (ITPRIPL1), a natural ligand of CD3ε, is implicated in tumor-immune interactions and is overexpressed in several solid tumors. However, its expression and functional significance in osteosarcoma and chordoma remain uncharacterized. This study aimed to evaluate CD3L1 expression in osteosarcoma and chordoma and assess its association with clinical features and outcomes. Formalin-fixed, paraffin-embedded tissue samples from 42 osteosarcoma and 20 chordoma patients were analyzed for CD3L1 expression using immunohistochemistry. Multiplex immunofluorescence staining was performed to evaluate immune cell infiltration in chordoma. Associations between CD3L1 expression and clinicopathological parameters were examined using chi-square tests, Fisher’s exact test, and Kaplan-Meier survival analysis. CD3L1 was detected in 62.9% (39/62) of cases, with positivity rates of 59.6% in osteosarcoma and 70.0% in chordoma. CD3L1 expression was independent of patient age, sex, or tumor location but was significantly associated with chondroid stroma and prior PD-1 immunotherapy in osteosarcoma. In chordoma, higher CD3L1 expression correlated with increased infiltration of CD8⁺ T cells, B cells, and M2 macrophages. CD3L1 is expressed in osteosarcoma and chordoma and is associated with features of the tumor immune microenvironment, including markers of macrophage infiltration. As a potential therapeutic target, CD3L1 warrants further functional and clinical investigation.

Purpose CD3L1 (ITPRIPL1), a natural ligand of CD3ε, is implicated in tumor-immune interactions and is overexpressed in several solid tumors. However, its expression and functional significance in osteosarcoma and chordoma remain uncharacterized. This study aimed to evaluate CD3L1 expression in osteosarcoma and chordoma and assess its association with clinical features and outcomes. Methods Formalin-fixed, paraffin-embedded tissue samples from 42 osteosarcoma and 20 chordoma patients were analyzed for CD3L1 expression using immunohistochemistry. Multiplex immunofluorescence staining was performed to evaluate immune cell infiltration in chordoma. Associations between CD3L1 expression and clinicopathological parameters were examined using chi-square tests, Fisher’s exact test, and Kaplan-Meier survival analysis. Results CD3L1 was detected in 62.9% (39/62) of cases, with positivity rates of 59.6% in osteosarcoma and 70.0% in chordoma. CD3L1 expression was independent of patient age, sex, or tumor location but was significantly associated with chondroid stroma and prior PD-1 immunotherapy in osteosarcoma. In chordoma, higher CD3L1 expression correlated with increased infiltration of CD8⁺ T cells, B cells, and M2 macrophages. Conclusion CD3L1 is expressed in osteosarcoma and chordoma and may play a pivotal role in regulating tumor stroma and the immune microenvironment, representing a potential target for future therapeutic strategies.

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.