PD-L1 is one of the most critical immune checkpoint proteins, inhibiting T-cell immune responses by binding to PD-1. This study aims to validate that allicin can regulate PD-L1 expression through the IL-6/JAK2/STAT3 pathway, thereby inhibiting immune evasion in osteosarcoma.

We screened differentially expressed genes associated with prognosis using the GEO database and identified the IL-6/JAK2/STAT3/PDL1 pathway through KEGG and GO enrichment analysis. We established the HOS human osteosarcoma cell line and the K7M2 mouse osteosarcoma cell line. Both cell lines were treated with allicin at concentrations of 12.5, 25, and 50 μmol/L. Transwell, clonogenic, and scratch assays validated allicin's inhibitory effects on osteosarcoma cell growth, migration, and invasion. Western Blot assays measured expression levels of key proteins including IL-6, JAK2, STAT3, PD-L1, and phosphorylated JAK2/STAT3. Animal models were established in Balb/c mice and treated with allicin. Mouse clinical signs, tumor volume, and size were recorded. Tumor microenvironment and immune cell infiltration markers (CD3+, CD4+, CD8+, IFN-γ, granzyme B) were analyzed via flow cytometry and immunofluorescence. Immunofluorescence and immunohistochemistry were employed to detect the expression of PD-L1, CD8, and other relevant markers in mouse tumor models, validating allicin's inhibitory effect on immune evasion.

In osteosarcoma cell lines treated with allicin, the IL-6/JAK2/STAT3 signaling pathway was downregulated, and PD-L1 expression was significantly suppressed. In allicin-treated mice, recruitment of CD4+ and CD8+ T cells increased, IFN-γ and granzyme B expression enhanced, and tumor immune evasion was markedly inhibited.

Allicin suppresses PD-L1 expression by modulating the IL-6/JAK2/STAT3 signaling pathway, thereby improving the tumor microenvironment and inhibiting immune evasion in osteosarcoma cells. This study demonstrates the potential of allicin as an adjunct to immunotherapy.

Head and neck squamous cell carcinoma (HNSC) is one of the most prevalent malignancies worldwide. PRKAR1B, a regulatory component of protein kinase A (PKA), has been widely investigated for its potential involvement in tumorigenesis across different diseases. However, its specific role in HNSC remains elusive. In this study, significant differences in PRKAR1B expression were observed across various cancer types. PRKAR1B was highly expressed in HNSC and was strongly associated with poor prognosis in HNSC patients. Moreover, it was identified as an independent prognostic factor significantly associated with clinical parameters. Correlation analysis revealed that PRKAR1B expression was associated with genes such as C7orf50, EIF3B, TBRG4, DDX56, and BRAT1. Additionally, it was associated with TMB and was correlated with the infiltration of immune cells such as M1 macrophages, activated mast cells, and eosinophils. Notably, PRKAR1B was identified as a predictive marker for the efficacy of CTLA-4 inhibitors, with high PRKAR1B expression potentially conferring superior therapeutic responses. Drug sensitivity analysis further suggested that Lapatinib and Erlotinib may be beneficial in HNSC patients with high PRKAR1B expression. Meanwhile, in vitro experiments showed that PRKAR1B knockdown inhibited HNSC cell proliferation and migration. Lastly, PRKAR1B protein expression was upregulated in clinical HNSC samples. Overall, this study thoroughly examined PRKAR1B expression and its prognostic significance in HNSC, investigated related molecular pathways and immune cell interactions, and validated its role via in vitro experiments.

Radiofrequency ablation (RFA) has emerged as a commonly used approach for early-stage hepatocellular carcinoma (HCC) patients. Exploring immunity changes after RFA therapy is helpful for reducing recurrence.

In this study, we enrolled 12 patients with HCC with their 47 blood samples, including before and after complete RFA therapy. We performed an integrative analysis of the transcriptome and methylome, investigated using a novel self-developed methylation array (HYGEIA panel). Core analyses included differential analyses of both transcriptome and methylome, DIABLO-based multi-omics integration, gene set enrichment analysis, and time-series gene clustering with visualization.

Our study elucidated the complex effect of the location of CpG site methylation on their corresponding gene transcription; 58.44% of CpG sites were located in the promoter (≤1 kb) region and mainly negatively correlated with gene expression. RFA treatment in HCC patients activated antigen processing and presentation and Th1 and Th2 cell differentiation signaling pathways. The anti-tumor immune responses induced by RFA therapy persisted for less than 9 months in recurrent patients. Meanwhile, the ability of T-cell differentiation in HCC patients was a potential factor to prevent recurrence.

These findings elucidated the dynamic peripheral immune remodeling post-RFA and identified host T-cell fitness as a key determinant of recurrence, providing a rationale for combining RFA with immunotherapy to prolong protective immune responses.

Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma, and is associated with poor prognosis. A better understanding of the role of PD-1⁺CD8⁺ T cells in the pleural environment and their relevance to patient survival could facilitate better clinical decision-making.

We performed a cohort study involving NSCLC patients with MPE. The abundance of pleural PD-1⁺CD8⁺ T cells was measured using flow cytometry. We also assessed the presence of epidermal growth factor receptor (EGFR) mutations and programmed death-ligand 1 (PD-L1) expression in the pleural fluid. The LENT score, a known prognostic tool, was combined with pleural PD-1⁺CD8⁺ T cell abundance to develop a novel scoring system, the Immuno-LENT score. The model's performance was validated using the bootstrap method and concordance index (C-index) calculation.

We found that PD-1⁺CD8⁺ T cells were present in the pleural fluid of all patients with MPE. Notably, the abundance of these cells was influenced by EGFR mutations, while PD-L1 expression had little effect. Patients with a higher abundance of pleural PD-1⁺CD8⁺ T cells also exhibited higher LENT scores, correlating with poorer survival. The Immuno-LENT score, incorporating both the LENT score and pleural PD-1⁺CD8⁺ T cell abundance, was found to be an independent prognostic factor. The model showed strong statistical robustness with a high C-index.

The combination of pleural PD-1⁺CD8⁺ T cells with the LENT score offers a more accurate prognostic tool for survival prediction in NSCLC patients with MPE. Our findings suggest that the Immuno-LENT score could guide clinical management and inform therapeutic decisions for these patients, improving patient outcomes by tailoring interventions based on a more comprehensive biomarker profile.

The tumor microenvironment (TME) is critical for liver cancer progression and therapy response. As a key RNA modification, 5-methylcytosine (m⁵C) methylation is implicated in this process, yet the molecular mechanisms by which m⁵C modification mediates intercellular crosstalk within the TME remain less understood.

The m⁵C methylomes in wildtype and m⁵C-catalyzing enzyme NSUN2-perturbed liver cancer cells were profiled via MeRIP-seq. GAT-MeRIP, a graph attention neural network-based algorithm, was developed to identify functional m⁵C-modified target genes from MeRIP-seq data. TME-related functional m⁵C targets were screened through cell-cell communication analysis of single-cell transcriptomic data. In vitro functional validation of the key target gene was performed via a combination of cell co-culture, qRT-PCR, MeRIP-qPCR, ELISA, and flow cytometry assays. Additionally, public liver cancer cohort data were used for clinical correlation and prognostic analysis.

Angiotensinogen (AGT) was identified as a key m⁵C-regulated secretory factor contributing to tumor-microenvironment communication in liver cancer. NSUN2 knock-down increased AGT's expression and enhanced cytotoxicity of co-cultured NK cells, which can be canceled by AGT-neutralizing antibody. Exogenous AGT treatment significantly enhanced NK cell cytotoxicity by upregulating IFN-γ, TNF-α, and perforin, as well as the proportion of CD107a⁺ NK cells. Liver cancer patients with low NSUN2 and high AGT exhibited significantly improved overall survival rates and higher immune infiltration.

This study unveils novel regulatory function of m⁵C-modified AGT in modulating the liver TME that could be helpful for improving liver cancer prognosis and immunotherapy.

Histiocytic sarcoma (HS) is a rare neoplasm derived from non-Langerhans histiocytic cells, exceptionally arising from B-ALL.

We present the case of a child with high-risk B-ALL with PAX5 P80R mutation.

Despite initial remission, a chemoresistant paravertebral mass was identified as HS. A shared IGK/TCRB rearrangements and PAX5 alterations between the leukaemic and histiocytic clones suggested transdifferentiation driven by PAX5. A somatic MAP2K1 mutation in the HS component prompted selumetinib treatment, leading to a rapid response.

This case underscores the role of PAX5 in lineage plasticity and highlights the potential of targeted MEK inhibition in MAPK-driven HS arising from B-ALL.

The authors have confirmed clinical trial registration is not needed for this submission.

With the launch of two Norwegian proton facilities, Norwegian Neuro-Oncology Interest Group developed consensus guidelines for selection of neuro-oncology patients to proton therapy. Relevant literature review and nationwide discussions informed the process. An overview of patients offered proton therapy during the first six months of operation was registered.

Gut microbiota and their metabolites are essential for a wide range of human physiological processes, including inflammation, immunity, and homeostasis. The intricate interplay between gut microbiota and the host immune system profoundly influences both the therapeutic response and the immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitors (ICIs) therapy. Prior evidence has established the rationale for modulating the gut microbiota to improve the incidence and prognosis of ICI-associated myocarditis. In the future, we may prevent or treat ICI-associated myocarditis by regulating the gut microbiota through methods such as microbiota transplantation, antibiotic regimens, or probiotic supplements. But there is still a considerable distance between research and clinical practice.

We developed CARING to support neuro-oncology caregivers. CARING includes eSNAP, a web-based tool to identify social support resources, and 8 weeks of individual phone-based non-clinical navigation focused on support identification and coping skills. This study aimed to evaluate the efficacy of CARING on caregiver and patient psychosocial outcomes.

We compared CARING to a waitlist control (WLC) in an RCT. Neuro-oncology patients and their caregivers were recruited from a National Cancer Institute (NCI)-designated comprehensive cancer center in Florida from February 2020 to June 2024. Eighty-one caregivers were assigned to CARING and 35 to WLC. All participants completed baseline measures, including demographics and health data. Primary outcomes collected at 8 weeks were caregiver support and self-efficacy. Secondary outcomes were caregiver burden, personal gain, and caregiver and patient anxiety and depressive symptoms. General Linear Mixed Models examined changes in outcomes from baseline to 8 weeks by condition.

No significant demographic differences existed between conditions. CARING caregivers reported significantly lower ratings of stress/frustration compared to feeling in control/hope (F(1,92) = 6.19, P = .015) at 8 weeks compared to WLC. There was a significant increase in personal gain (M = 0.7, SD = 2.5, t(63) = 2.13, P = .037) and a marginally-significant increase in self-efficacy (M = 1.6, SD = 6.6, t(61) = 1.88, P = .065) for CARING caregivers at 8 weeks. Although the intervention is targeted only at caregivers, patients of CARING caregivers reported marginally significantly fewer depressive symptoms (F(1,51) = 2.89, P = .096) at 8 weeks compared to WLC.

CARING decreases the ratio of negative to positive emotions and perceptions of personal gain in caregivers at 8 weeks, compared to WLC.

Intracranial gliosarcoma (GSM) is a rare and aggressive variant of glioblastoma, characterized by a dismal prognosis and high rates of early recurrence and metastasis. Preoperative differentiation from other neoplasms based on imaging features remains a significant clinical challenge. The current study reports the case of a 55-year-old female who presented with a headache as the primary clinical symptom. The patient underwent brain MRI due to progressively worsening symptoms of diplopia, intermittent dull headaches localized to the right occipital region and an unsteady gait. Preoperative magnetic resonance imaging revealed a large, lobulated mass in the right cerebellar hemisphere extending into the parahippocampal region. The diagnosis of WHO Grade IV GSM was confirmed by postoperative histopathological and immunohistochemical analysis, which revealed a biphasic pattern with glial fibrillary acidic protein-positive glial and smooth muscle actin/vimentin-positive sarcomatous components, alongside a high Ki-67 proliferation index of 30%. The patient underwent a subtotal resection followed by adjuvant radiotherapy with concurrent temozolomide chemotherapy. Despite this multimodal treatment, follow-up imaging demonstrated tumor recurrence at 2 months, with significant further progression and brain herniation observed at the 12-month follow-up. The present case underscores the diagnostic challenges and aggressive clinical course of GSM, particularly when located in the cerebellum. The rapid recurrence despite combined-modality therapy highlights the need for improved diagnostic strategies and more effective treatment protocols for this formidable disease.