V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint protein that impairs antitumor T cell responses. While broadly expressed on myeloid cells and T cells, the specific contribution of T cell-intrinsic VISTA to antitumor immunity remains undefined. This study investigated the phenotypic and functional consequences of T cell-specific VISTA deletion in tumor-specific CD8+ T cells. Single-cell transcriptomic analysis, TCR repertoire profiling, and flow cytometry revealed that loss of T cell-intrinsic VISTA enhanced early priming and short-term expansion of CD8+ T cells, yet this initial advantage failed to confer durable tumor control. Persistent dysfunction in VISTA-deficient T cells was in part driven by trans-VISTA on myeloid cells, while CTLA-4 upregulation further constrained T cell responses. T cell-intrinsic VISTA deficiency cooperated with CTLA-4 blockade to improve T cell survival and broaden TCR repertoire diversity, resulting in more robust tumor regression than CTLA-4 inhibition alone. A transcriptional signature enriched in VISTA-deficient cytotoxic T cells correlated with favorable outcomes in cancer patients treated with existing immune checkpoint inhibitors. These findings collectively define T cell-intrinsic mechanisms by which VISTA enforces T cell dysfunction and underscore its potential as both a therapeutic target and a biomarker of resistance to current immunotherapies.

This study explores a nanoparticle-based delivery system for alisertib, a selective aurora kinase A (AURKA) inhibitor. This nanocomplex is designed to enhance tumor-specific delivery. AURKA is overexpressed in various cancers, including atypical teratoid/rhabdoid tumors (ATRTs) and is associated with poor clinical outcomes. Alisertib has demonstrated promising efficacy in multiple preclinical studies, which supported its advancement into clinical trials across various cancer types. However, alisertib has not met key efficacy endpoints primarily due to its poor biodistribution to tumors and inadequate penetration of biological barriers, including the blood-brain barrier (BBB). Our study aims to address these issues.

The efficacy of chemotherapy for treating lung cancer is hindered by insufficient intracellular drug utilisation. Moreover, non-targeted distribution often leads to severe side effects, resulting in poor prognosis and low patient compliance. Therefore, a more effective strategy is required to achieve effective treatment. In this study, we aimed to develop a pH-responsive nanoplatform for intratracheal administration to enhance drug accumulation in lung cancer tissues and promote the accumulation of drugs within tumour cells.

The aim of this work is to synthesize magnesium oxide nanoparticles (Gi-MgO NPs) by extracting 6-gingerol (Gi) from Zingiber officinale rhizomes. The Gi-MgO NPs were further investigated for anticancer, anti-inflammatory, and antioxidant activities.

To perform a cross-sectional analysis of the indication expansion trends and pivotal trial features of novel multi-indication anti-cancer drugs approved in China from 2000 to 2024.

The management of advanced endometrial cancer (EC) has been transformed by immunotherapy, raising a pivotal clinical challenge: selecting patients with mismatch repair-deficient (dMMR) disease for intensive dual PD-1/CTLA-4 blockade versus standard PD-1 monotherapy. We conducted a narrative review of phase II/III clinical trials and key translational studies published up to 2023 to critically appraise current evidence. In dMMR EC, the conventional ipilimumab-nivolumab combination yields higher objective response rates (ORR ≈ 63%) than PD-1 monotherapy (ORR ≈ 48%) but is associated with a substantially increased incidence of grade ≥ 3 immune-related adverse events (≈ 23% vs. ≈ 12%). The development of bispecific antibodies like cadonilimab, which demonstrates robust efficacy with a lower incidence of high-grade toxicity (grade ≥ 3 treatment-related adverse events: 8.3%), presents a promising strategy to improve the therapeutic index. For clinicians, the current decision-making process must be highly individualized, weighing factors such as tumor burden, pace of disease, and patient tolerance for toxicity in the absence of validated biomarkers to guide treatment intensity beyond dMMR status. We also addressed the critical importance of accurate MMR/MSI testing and the clinical implications of a well-documented methodological discordance rate. In contrast, for patients with mismatch repair-proficient (pMMR) tumors, the evidence firmly supports alternative regimens, such as lenvatinib plus pembrolizumab, over dual PD-1/CTLA-4 blockade. Navigating the evolving landscape of immunotherapy in EC requires a nuanced, patient-centric approach. The integration of novel bispecific antibodies may soon simplify the balance between efficacy and toxicity, but until then, treatment selection remains a deliberate process, underscoring the gynecologic oncologist's pivotal role in personalizing care.

Immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with advanced non-small cell lung cancer (NSCLC), but may rarely trigger severe immune-related adverse events (irAEs).

The response rate to immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) varies significantly among individuals. Cancer-associated macrophages (TAMs) are key components of the tumor immune microenvironment (TIME), influencing tumor proliferation, metastasis, immune cell recruitment, and activation through diverse mechanisms. Their high heterogeneity, particularly in the context of immunotherapy, warrants further investigation.

Gastric cancer is among the most prevalent malignant tumors of the digestive system worldwide. In recent years, immune checkpoint inhibitors (ICIs) have achieved substantial advances in the treatment of gastric cancer. By blocking the PD-1/PD-L1 and CTLA-4 signaling pathways, ICIs enhance antitumor immune responses and offer novel therapeutic options for patients. However, their clinical application continues to face significant challenges, including therapeutic resistance, immune-related adverse events, the lack of reliable biomarkers, and an immunosuppressive tumor microenvironment. This narrative review summarizes recent advances in ICIs-based therapies for gastric cancer, provides an in-depth analysis of existing clinical challenges, and highlights key future research directions, including biomarker discovery, development of predictive models, optimization of combination regimens, targeting of resistance mechanisms, modulation of the tumor-associated microbiota, and improved toxicity management. Moving forward, efforts should focus on advancing immunotherapy toward individualized and precision-based approaches to maximize both efficacy and safety, thereby enabling further optimization and breakthroughs in gastric cancer immunotherapy.

Although immune checkpoint inhibitors (ICIs) have improved survival in head and neck squamous cell carcinoma (HNSCC), associated adverse events, such as sialadenitis, remain poorly characterized. This study aimed to define the clinicopathological features, establish the causal pathogenic mechanism, and validate a therapeutic target for ICI-associated sialadenitis.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the clonal expansion of immature lymphoblastic cells. Treating patients with disease relapse is challenging, especially after allogeneic stem cell transplantation (aSCT). Although the CD19xCD3 bispecific antibody (bsAb) blinatumomab has improved outcomes for patients with relapsed B-ALL, T cell exhaustion and immune-associated treatment side effects remain problematic. Vγ9Vδ2 T cells constitute a relatively small subset in healthy individuals but their abundance increases after aSCT, and higher numbers correlate with improved outcomes. Unlike ab T cells, Vγ9Vδ2 T cells are not allo-reactive, do not contribute to graft-versus-host disease and release fewer inflammatory cytokines.

Immune checkpoint inhibitors (ICIs) targeting PD-1 have revolutionized melanoma treatment, yet their clinical efficacy is frequently limited by immune-related adverse events (irAEs). The underlying mechanisms of irAEs remain poorly defined, particularly in the acral melanoma subtype.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is the leading cause of cancer-related deaths worldwide. The majority of patients with HCC are diagnosed at an advanced stage, resulting in limited treatment options. In recent years, numerous clinical trials have confirmed that immunotherapy, particularly anti-programmed cell death 1 (anti-PD-1)/programmed cell death ligand 1 (PD-L1), has emerged as a promising treatment for advanced HCC. However, in real-world practice, the clinical efficacy of adding immunotherapy to locoregional therapies remains unknown, representing a knowledge gap.

Chemotherapy-induced neutropenia (CIN) remains a major dose-limiting toxicity associated with myelosuppressive chemotherapy regimens. The development of therapeutic strategies capable of effectively restoring neutrophil production and function could address a critical unmet clinical issue. ZGSII, a bioactive compound derived from Sanguisorba officinalis, has shown potential in ameliorating leukopenia. To further evaluate its therapeutic applicability for CIN, a comprehensive understanding of its underlying mechanisms is essential. This study aims to assess the efficacy of ZGSII in mitigating cyclophosphamide-induced neutropenia and myelosuppression and to elucidate the underlying mechanism involved through transcriptome sequencing, protein-protein interaction network construction, and functional validation assays.

Immunotherapy employing immune checkpoint inhibitors (ICIs) represents a pivotal approach for the management of recurrent and metastatic head and neck cancers (HNCs). Ipilimumab is a fully human monoclonal IgG1κ antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), which can be introduced as a monotherapy or dual immunological regimen with nivolumab (anti-programmed death protein 1, PD-1). The background of the use of these monoclonal antibodies as combination immunotherapy is strongly associated with their different mechanisms of action. CTLA-4 and PD-1 are able to regulate the function of T cells through different mechanisms. Despite the better efficacy of immunotherapy with ipilimumab + nivolumab in HNCs observed in some cases, the overall effect regarding the comparison of ipilimumab versus ipilimumab + nivolumab is still unclear. The microbiome is one of the biomarkers that affect the response to immunotherapy with ICIs, including ipilimumab. Nevertheless, there is a clear lack of data in this context with regard to HNCs. The beneficial signature of the microbiome contributes to the prevention of the immune-related adverse events caused by ipilimumab. Notably, the incidence of gastrointestinal side effects induced by ICIs is significantly increased in the dual regimen with ipilimumab + nivolumab, which affects its recommendation for patients with HNCs.

Chemotherapy-induced alopecia (CIA) is known to have a significant psychological and quality of life impact. Although cold caps have been shown to prevent CIA, expense and extension of treatment durations are barriers for routine clinical use. Keratinocyte growth factor (KGF) has been shown to have cytoprotective effects on human hair follicles and reduce alopecia in preclinical models. We hypothesized that KGF-hair serum (KGF-HS) will prevent CIA.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, largely due to metastasis and therapeutic resistance. Beauvericin, a cyclohexadepsipeptide mycotoxin produced by Beauveria and Cordyceps species, has demonstrated anticancer activity in multiple malignancies; however, its mechanistic effects in CRC have not been fully defined. In this study, we investigated the cellular and molecular effects of beauvericin in HCT116 and SW480 CRC cells using in vitro models. Beauvericin reduced cell viability and clonogenic growth, induced G0/G1 cell-cycle arrest, and activated mitochondria-dependent apoptosis through modulation of Bcl-2 family proteins and caspase activation. At sub-cytotoxic concentrations, beauvericin significantly suppressed migratory and invasive phenotypes and attenuated epithelial-mesenchymal transition (EMT)-associated features, accompanied by reduced activation of integrin α6/FAK/Src/ERK1/2 signaling without altering total protein expression. Conditioned medium from beauvericin-treated CRC cells markedly inhibited endothelial proliferation, invasion, and tube formation, coinciding with reduced VEGF secretion. Network-based target prediction and immunoblot validation further demonstrated that beauvericin treatment was associated with decreased phosphorylation of JAK2, STAT1, and STAT3. Collectively, these findings indicate that beauvericin modulates multiple malignant phenotypes of CRC cells in vitro by inducing mitochondrial apoptosis and attenuating EMT-associated signaling, VEGF-dependent endothelial activation, and JAK/STAT pathway activity. These results provide mechanistic insight into the anti-tumor potential of beauvericin and support further preclinical evaluation.

Melanoma represents a highly aggressive and immunotherapy-resistant malignancy with limited immunotherapy efficacy, underscoring the urgent need for novel treatment strategies that integrate precise diagnosis and potent immunomodulation. The combination of photothermal therapy (PTT) and STING pathway activation has emerged as a promising approach to potentiate antitumor immunity. Nevertheless, it remains challenging to integrate real-time deep-tissue imaging with spatiotemporally synchronized immunostimulation within a single nanoplatform, especially for the effective treatment of advanced melanoma.

Uveal melanoma (UM) is the primary intraocular malignancy in adults and has an extremely poor prognosis due to a high rate of metastasis. Because current drug options are generally ineffective, there is an urgent need for new agents with anti-UM efficacy. The phenylcyclohexyl-urea UC2288 was investigated in in vitro, ex vivo and in vivo UM models. The anti-cancer actions of UC2288 were evaluated using cell viability and cell death assays. Tumour migration, invasion and reproductive cell growth assays were used to assess the anti-metastatic potential of UC2288. Such effects were corroborated in primary cultures derived from patient tumours and in vivo in a UM cell xenograft mouse model. UC2288 decreased UM cell proliferation in conventional and 3-dimensional cell culture by disrupting cell cycle progression and modulating cyclin expression. UC2288 also targeted the mitochondrion and increased the production of reactive oxygen species, which promoted necrotic cell death. In mechanistic studies, UC2288 activated AMPK and downstream eIF2/ATF pathways of ER stress and autophagy in UM cells. UC2288 also impaired UM cell migration, invasion and reproductive growth, which is consistent with anti-metastatic activity. These findings were replicated in vivo in a UM cell xenograft model. Taken together, UC2288 represents a promising candidate for further development that targets UM tumours with favourable anti-cancer effects.

Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20-30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN.