This work aimed to investigate tumor-infiltrating immune cells (TIICs) and immune-associated genes in the tumor microenvironment of osteosarcoma. An algorithm known as ESTIMATE was applied for immune score assessment, and osteosarcoma cases were assigned to the high and low immune score groups. Immuneassociated genes between these groups were compared, and an optimal immune-related risk model was built by Cox regression analyses. The deconvolution algorithm (referred to as CIBERSORT) was applied to assess 22 TIICs for their amounts in the osteosarcoma microenvironment. Osteosarcoma cases with high immune score had significantly improved outcome (P<0.01). The proportions of naive B cells and M0 macrophages were significantly lower in high immune score tissues compared with the low immune score group (P<0.05), while the amounts of M1 macrophages, M2 macrophages, and resting dendritic cells were significantly higher (P<0.05). Important immune-associated genes were determined to generate a prognostic model by Cox regression analysis. Interestingly, cases with high risk score had poor outcome (P<0.01). The areas under the curve (AUC) for the risk model in predicting 1, 3 and 5-year survival were 0.634, 0.781, and 0.809, respectively. Gene set enrichment analysis suggested immunosuppression in high-risk osteosarcoma patients, in association with poor outcome.

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BackgroundThe national Comprehensive Cancer Network has suggested pembrolizumab as a second-line therapy for esophageal squamous cell carcinoma (ESCC) patients with a programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10. However, despite the increased survival rate associated with pembrolizumab in these patient population, the high cost of pembrolizumab may influence its antitumor effect. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared to chemotherapy as second-line treatments for esophageal carcinoma (EC) based on KEYNOTE-181 trial.MethodsA Markov model was constructed using TreeAge 2021 based on three different groups: all intent-to-treat patients (ITT population), patients with ESCC (ESCC population), and patients with a PD-L1 CPS ≥10 (CPS ≥10 population). Incremental cost, Incremental effect, Life-years, quality-adjusted life-years (QALYs) and incremental cost–effectiveness ratio (ICER) were calculated. Analyses were conducted on the setting of a willingness-to-pay threshold of $150,000 from the US perspective.ResultsThe ICERs for pembrolizumab were $157,589.545 per QALY, $60,238.823 per QALY, and $100,114.929 per QALY compared with chemotherapy in the ITT, ESCC, and CPS≥10 populations, respectively. The ICER of the ITT population was higher than $150,000, suggesting that pembrolizumab was not a cost-effective treatment scheme in patients with a PD-L1 CPS ≤ 10 or esophageal adenocarcinoma. The ICER was &lt; $150,000 in the ESCC and CPS≥10 populations, indicating that pembrolizumab was cost-effective in these two subgroups.ConclusionThe determining of pembrolizumab as a cost-effective second-line therapy for EC in the United States depends on the histologic type and PD-L1 expression.