Combination therapy targeting the PD-1/PD-L1 and TIGIT pathways has been explored to enhance the efficacy of current immunotherapies. In this study, we investigated strategies to further potentiate the co-blockade of PD-L1 and TIGIT for cancer immunotherapy. Firstly, we demonstrated that the bispecific antibody (HB0036) for PD-L1 and TIGIT co-blockade induced a greater T-cell proliferative response in vitro compared to the combined administration of the parental antibodies. This response was associated with CD226 upregulation and PD-1 downregulation. HB0036 significantly enriched the TIGIT antibody at PD-L1⁺ tumors and achieved improved tumor control with favorable immunological characteristics in both syngeneic and xenograft tumor models. Secondly, we showed that tumor control by co-targeting PD-L1 and TIGIT can be further enhanced by additionally blocking VEGF, a key player in tumorigenesis and tumor angiogenesis, in preclinical studies. Lastly, considering the heterogeneity of tumors, we analyzed how the expression patterns of PD-L1 and CD155 influence T cell responses. We also examined the spatial distribution of PD-L1 and CD155, along with related immunological parameters from patient samples, to assess the potential of PD-L1 and TIGIT co-blockade in diverse tumor contexts.

Immune-related adverse events, notably arthritis (irAE-arthritis), frequently occur in patients receiving immune checkpoint inhibitors. Arthritis severity varies from mild to severe, adversely impacting quality of life. Despite reports in clinical trials and real-world studies, the pathophysiology and optimal management of irAE-associated arthritis (irAE-arthritis) are still unclear.

From the inception to September 25, 2025, a search was conducted on PubMed, EMBASE, and MEDLINE for case reports/series on irAE-arthritis.

The most common rheumatic irAEs were arthritis. Various rheumatic syndromes have been reported, such as arthralgia, mono-/oligo-/polyarthritis, reactive and psoriatic arthritis, RS3PE, tenosynovitis. The onset of irAE-arthritis is attributed to T cell dysregulation, B cell activation with autoantibody production, cytokine - mediated inflammation, and impaired immune tolerance due to Treg dysfunction. NSAIDs, intra-articular/systemic corticosteroids, csDMARDs, and biologics play key roles in irAE-arthritis management, and JAK inhibitors may emerge as a significant therapeutic strategy in the future.

Given the increasing use of immunotherapy in oncology and other fields, developing a comprehensive understanding of irAE-arthritis is crucial. This review aims to provide an in-depth overview of current knowledge on irAE-arthritis, including its epidemiology, clinical presentation, underlying mechanisms, and management approaches.

Immune checkpoint molecules play a central role in regulating T cell function, maintaining immune homeostasis, and facilitating tumor immune evasion, making them critical targets in cancer immunotherapy. This review provides a comprehensive overview of the structural characteristics and signaling mechanisms of key co-inhibitory and co-stimulatory molecules, and their immunoregulatory roles in both solid tumors and hematological malignancies. Recent advances in the clinical application of immune checkpoint inhibitors, combination therapy strategies, and mechanisms of resistance are discussed. Furthermore, the importance of multi-target combinatorial approaches and personalized immune modulation is emphasized, offering valuable insights and directions for optimizing cancer immunotherapy strategies.

Artificial intelligence (AI) tools based on large language models (LLMs) are being increasingly used by researchers and may play a role in health-related research priority-setting exercises (RPSEs). However, little is known about how these tools may differ in the types of research priorities they generate.

We examined research priorities aimed at improving treatments for four diseases: cancer, COVID-19, HIV, and Alzheimer. We compared the outputs from five AI tools (DeepSeek, ChatGPT, Claude, Perplexity, and Gemini) using SBERT-BioBERT embeddings and cosine similarity scores, and assessed the stability of differences between them by re-running identical prompts and slightly modified versions.

We found that the outputs produced by Gemini were highly similar to those produced by the other tools. The two most different outputs were those produced by DeepSeek and Perplexity, whereby the former tended to emphasise technical medical issues, while the latter emphasised public health concerns. This substantive distinction between DeepSeek and Perplexity remained stable across repeated and tweaked prompts.

Our exploratory analysis suggests that Gemini performs well for researchers who prefer to generate health-related research priorities using a single AI model. For those planning to draw on multiple models, Perplexity and DeepSeek offer complementary perspectives.

Lymph node (LN) metastasis is a well-established independent prognostic factor in head and neck squamous cell carcinoma (HNSCC). Formation of suppressive tumour immune microenvironment (TIME) is a major contributor to tumour immune evasion and metastasis. However, the TIME landscape underlying LN-metastatic HNSCC remains poorly elucidated.

A total of 688 866 single-cell transcriptomes across 212 HNSCC samples were integrated. Comprehensive bioinformatic analyses on single-cell RNA sequencing and microarray datasets revealed a TREM2⁺ tumour-associated macrophage (TAM) cluster associated with LN metastasis. The functional role of TREM2⁺ TAMs was investigated through multiplex immunohistochemistry (mIHC) staining in clinical HNSCC cohort and in vitro co-culture experiments. Furthermore, machine learning algorithms were employed to construct a prognostic model for HNSCC.

Integrative single-cell analysis revealed the immunosuppressive TIME of LN-metastatic HNSCC, characterised by high infiltration of exhausted CD8⁺ T cells (CD8⁺ Tex). We identified a specific TREM2⁺ TAM cluster that was strongly associated with CD8⁺ Tex infiltration and LN metastasis. In vitro experiment confirmed that TREM2⁺ TAMs promoted CD8⁺ T cell exhaustion. Mechanistically, TREM2⁺ TAMs exhibited a terminally differentiated phenotype driven by ETV5, and secreted SPP1 to interact with CD44 on CD8⁺ T cells, thus upregulating BHLHE40 to promote CD8⁺ Tex formation. Clinically, a prognostic model based on TREM2⁺ TAM signature genes was trained to independently predict HNSCC outcomes.

This study delineates the mechanism that TREM2⁺ TAMs promote LN metastasis in HNSCC by facilitating CD8⁺ T cells exhaustion via SPP1-CD44-BHLHE40 axis, proposing TREM2⁺ TAMs as potential therapeutic target for HNSCC.

This phase I/II study aimed to evaluate the tolerability and the organ-sparing effects of continuous positive airway pressure (CPAP) in breast cancer radiotherapy (RT).

We conducted a prospective, single-institutional trial approved by the Ministry of Food and Drug Safety of South Korea. Patients with breast cancer who received postoperative RT underwent 4D-CT simulation and treatment planning under both free breathing (FB) and CPAP-assisted breathing (WC), with a target pressure of 20 cm H2O. Adverse events (AEs) were evaluated, and dosimetric parameters of organs at risk and heart position change were compared between the FB and WC arms.

Among 20 enrolled patients, four withdrew due to discomfort during simulation. During the trial, no CPAP-related AEs greater than grade 2 were observed. Compared to FB, CPAP reduced the mean heart dose by 33.8% (p < 0.001), as well as V5-V30 for both the left ventricle and left anterior descending artery (all p < 0.05). It also led to significant reductions in V5-V40 and the mean ipsilateral lung dose, including a 4.4% reduction in V20 (all p < 0.001). The heart centroid shifted rightward (4.8 mm), ventrally (8.1 mm), and caudally (16.3 mm) with CPAP, displacing the heart away from the RT field.

CPAP demonstrated both safety and efficacy for breast cancer RT, achieving significant reductions in cardiac and pulmonary radiation exposure. These findings support further investigation of CPAP as a novel respiratory motion management strategy. Future studies are warranted to identify optimal CPAP pressure levels to facilitate broader clinical implementation.

Teratomas originate from pluripotent germ cells and differentiate into the 3 germ cell layers: endoderm, mesoderm, and ectoderm. Hence, these tumors arise most often in the gonads. Extragonadal teratomas are rare in veterinary medicine. Congenital oropharyngeal teratoma, also known as epignathus, is a neoplasm that has been reported in humans and a few veterinary species. We describe the clinical, gross, cytologic, and histopathologic features of an oropharyngeal teratoma in a neonatal Boer × Nigerian Dwarf goat that died within 4 h of birth, and briefly review extragonadal teratomas in veterinary species.

To investigate the clinical distribution patterns and clinicopathological characteristics of basal cell carcinoma (BCC) in Southwest China.

A retrospective analysis was conducted among 2016 patients diagnosed with BCC between April 2003 and May 2025. The study focused on lesion locations, facial distribution patterns, presentations of multiple BCCs, and histopathological features of BCC.

A total of 2016 patients with 2138 BCC lesions were included, comprising 881 males (43.70%) and 1135 females (56.30%). The median age at initial diagnosis was 65 years (range, 17-101 years). Only 70 (3.50%) patients were younger than 35 years, whereas 663 (32.89%) were older than 70 years. The incidence of BCC increased with age from the fifth to the eighth decade of life. Most lesions were located on the head/face (88.59%, 1894), and 80.64% (1724) occurred on the faces. The nose/perinasal area was the most common facial subregion (31.15%, 666), followed by the cheeks (20.91%), indicating a midface predilection. Clinically, nodular/ulcerative presentations predominated (65.20%, 1394). Histopathologically, the nodular cystic subtype was most common (71.94%, 1538). Multiple tumors (two to ten lesions) were observed in 36 patients, including three cases with basal cell nevus syndrome. Surgical resection was performed in 97.82% (1972) of patients, while Mohs micrographic surgery was used in 25 (1.24%) cases. The 5-year recurrence rate was 4.10%.

BCC predominantly affects older adults, with an increasing incidence in those aged 50-80 years, and shows a striking predilection for sun-exposed midfacial sites. Nodular/ulcerative lesions are the predominant clinical presentation, and nodular cystic type is the most common histological subtype. Surgery remains the mainstay of treatment; although recurrences were infrequent, their distribution supports risk-adapted management and long-term follow-up.

While cisplatin-based chemotherapy is pivotal for advanced bladder cancer, acquired resistance remains a major obstacle. This study investigates key molecular drivers of this resistance and potential reversal strategies.

We established GC (Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3 (UC3) cells. Transcriptomic and proteomic analyses identified differentially expressed molecules. Apoptosis and cell viability were assessed by flow cytometry and CCK-8 (Cell Counting Kit-8) assays, while RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) and Western blot analyzed gene and protein expression. Immunofluorescence evaluated FAK (Focal Adhesion Kinase) phosphorylation, and a xenograft mouse model validated the findings in vivo.

Integrated transcriptomic and proteomic analysis identified FN1 (fibronectin) as a consistently upregulated top candidate in resistant cells (T24-R transcript log₂FC = 2.8, protein log₂FC = 0.9; UC3-R transcript log₂FC = 3.7; all p < 0.001). Knockdown of FN1 reduced chemoresistance (Resistance Index: 5.2 in T24-R and 2.0 in UC3-R cells, p < 0.001) and enhanced apoptosis (approximately 4.5-fold in T24-R and 7.5-fold in UC3-R, p < 0.001). ITGB4 (Integrin Subunit Beta 4) was upregulated in resistant cells (transcript log₂FC: 4.2 in T24-R and 3.03 in UC3-R; protein log₂FC: 0.67 in T24-R; all p < 0.01). Critically, ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1, which was associated with increased FAK (Y397) phosphorylation.

Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling. Targeting this axis represents a promising strategy to overcome chemoresistance.

The current treatment options and therapeutic targets for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer (BrCA), are limited. This study aimed to identify novel biomarkers and transcriptional regulatory networks (TRN) inherent in TNBC samples.

We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas (TCGA) to compare triple-positive breast cancer (TPBC) with TNBC. TRN algorithms and virtual inference of protein-enriched regulon (VIPER) were used to identify master regulators and their target genes. Utilizing TNBC cells (MDA-MB-231 and MDA-MB-468), we validated the relationship of nuclear factor erythroid 2-like 3 (NFE2L3) and basic helix-loop-helix family member E 40 (BHLHE40) by performing a luciferase assay. The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots. The effect of these genes on cell proliferation and migration was studied using phenotypic assays.

Using computational approaches, we identified NFE2L3 as a master regulator with BHLHE40 as its target gene. NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity. Additionally, silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels. We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.

These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC, highlighting NFE2L3's role in regulating the oncogenic activity of BHLHE40 in TNBC cells.