Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have been identified as prognostic indicators in various malignances. This study compared the usefulness of platelet-lymphocyte ratio (PLR) with that of neutrophil-lymphocyte ratio (NLR) for predicting outcomes of patients who underwent radical resection for soft tissue sarcoma (STS). We included 222 STS patients in this retrospective study. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease free survival (DFS). In univariate analysis, elevated PLR and NLR were both significantly associated with decreased OS. In multivariate analysis, PLR (HR: 2.60; 95 % CI: 1.17–5.74, P = 0.019) but not NLR was still identified as independent predictors of outcome. Median OS was 62 and 76 months for the high PLR and low PLR groups, respectively. High PLR and NLR were both significantly associated with shorter DFS in univariate analysis, with median DFS of 18 and 57 months in the high PLR and low PLR groups. In multivariate analysis, elevated PLR (HR: 1.77; 95 % CI: 1.05–2.97, P = 0.032) was also related to decreased DFS. Our findings provide a new and valuable clue for diagnosing and monitoring STS. Prediction of disease progression is not only determined by the use of clinical or histopathological factors including tumor grade, tumor size, and tumor site but also by host-response factors such as performance status, weight loss, and systemic inflammatory response. They also significantly affect clinical outcomes. Thus, PLR can be used to enhance clinical prognostication. Furthermore, the PLR can be assessed from peripheral blood tests that are routinely available without any other complicated expenditure, thus providing lower cost and greater convenience for the prognostication. Elevated preoperative PLR as an independent prognostic factor is superior to NLR in predicting clinical outcome in patients with STS.

Coagulation and nutrition play important roles in cancer progression. The aim of the present study is to evaluate the prognostic value of the preoperative fibrinogen/albumin ratio (FAR) in surgical patients with soft tissue sarcoma (STS) and to compare this value with other inflammatory biomarkers. In addition, we investigated the relationship between FAR and the clinicopathological characteristics of STS patients. We included 310 STS patients in this retrospective study. Kaplan-Meier curves, univariate and multivariate Cox proportional models were used in the prognostic analyses. According to the receiver operating characteristic (ROC) analysis, the optimal FAR cut-off value was 0.0726. The FAR exhibited a greater area under the curve (AUC) value (0.680) than did the NLR and PLR. An elevated FAR (≥0.0726) was significantly associated with an old age, large tumor size, deep tumor location, high tumor grade, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with an increased FAR had a shorter median survival time and a lower 5-year overall survival (OS) rate than did those with a low FAR (61.0 vs115.8 months, P < 0.001; 56.7% vs 82.4%, P < 0.001, respectively). Multivariate analysis indicated FAR (Hazard ratio (HR) 1.907, 95% confidence interval (CI) 1.161–3.132, P < 0.001) to be an independent prognostic factor for OS, as were tumor depth, grade and PLR. Preoperative FAR is associated with tumor progression and can be considered an independent factor for OS of resected STS patients.

Sarcoma is a rare and heterogeneous class of mesenchymal malignancies with poor prognosis. Panobinostat (LBH589) as one of histone deacetylase (HDAC) inhibitors has demonstrated anti-tumor activity in patients with sarcoma, but its mechanisms remains unclear. Here, we found that LBH589 alone inhibited the proliferation and colony formation of soft tissue sarcoma (STS) cell lines. Transcriptome analysis showed that treatment with LBH589 augmented the NK cell-mediated cytotoxicity. Quantitative real-time PCR and flow cytometric analysis (FACS) further confirmed that LBH589 increased the expression of NKG2D ligands MICA/MICB. Mechanistically, LBH589 activated the Wnt/β-catenin pathway by upregulating the histone acetylation in β-catenin promoter. In vitro co-culture experiments and in vivo animal experiments showed that LBH589 increased the cytotoxicity of natural killer (NK) cells while Wnt/β-catenin inhibitor decreased the effects. Our findings suggest that LBH589 facilitates the anti-tumor effect of NK cells, highlights LBH589 an effective assistance drug in NK cell-based immunotherapies.

Neuroblastoma (NB) is one of the common solid tumors in childhood and poses a threat to the lives of children. Patients with advanced‑stage or recurrent NB have a poor prognosis. CUDC‑907, as a novel dual‑target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol‑3‑kinase (PI3K), has been proven to play an antitumor role in several types of tumors. However, the exact role of CUDC‑907 in NB remains unclear. In the present study, in vivo and in vitro assays were performed to investigate the anti‑NB activity of CUDC‑907. Pentraxin 3 (PTX3) small interfering RNA (siRNA) and PTX3 overexpression plasmid were transfected into cells to define the underlying mechanisms of CUDC‑907. Tumor tissues and clinical information were collected and immunohistochemistry (IHC) was conducted to analyze the association between the expression of HDAC1, HDAC2, HDAC3 and CD44, and the prognosis of patients with NB. The results indicated that CUDC‑907 significantly inhibited the proliferation and migration, and induced the apoptosis of NB cells, downregulating the expression level of MYCN, and suppressing the PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC‑907 suppressed the stem‑like properties of NB cells by inhibiting PTX3, a ligand and upstream protein of CD44. IHC revealed that the high expression of HDAC1, 2, 3 and CD44 was associated with a poor prognosis of patients with NB. On the whole, these findings indicate that CUDC‑907 may be developed into a possible therapeutic approach for patients with NB.

Rhabdomyosarcoma (RMS) is one of the most common solid tumors in children and adolescents. Patients with relapsed/refractory RMS have limited treatment options, highlighting the urgency for the identification of novel therapeutic targets for RMS. In the present study, aurora kinase B (AURKB) was found to be highly expressed in RMS and associated with unfavorable prognosis of patients. Functional experiments indicated that inhibition of AURKB significantly reduced RMS cell proliferation, induced apoptosis and ferroptosis, and suppressed RMS growth in vivo. The highly expressed AURKB in RMS contributes to the apoptosis and ferroptosis resistance of tumor cells through the nucleophosmin 1 (NPM1)/Sp1 transcription factor (SP1)/acyl-CoA synthetase long-chain family member 5 (ACSL5) axis. Furthermore, inhibition of AURKB exerted an anti-RMS effect together with vincristine both in vitro and in vivo, with tolerable toxicity. The above findings provide insights we believe are new into the tumorigenesis of RMS, especially with regard to apoptosis or ferroptosis resistance, indicating that AURKB may be a potential target for clinical intervention in patients with RMS.

Soft tissue sarcoma is characterized by its rarity and complexity, making it more difficult to conduct large clinical trials compared with other solid tumors. Also known as ‘cold tumors,’ sarcomas, especially advanced sarcomas, have poor responses to immunotherapy. Based on that, the results of two groundbreaking phase 2 clinical trials about neoadjuvant immunotherapy in patients with liposarcoma or undifferentiated pleomorphic sarcoma are encouraging. In this paper, we discuss the results of these clinical trials and the challenges we are facing to conduct neoadjuvant immunotherapy in sarcomas and call for further research to promote the development of it.