Compartment-specific immune and tumor markers associated with clinical outcomes in patients with and without sarcomatoid/rhabdoid renal cell carcinoma treated with ipilimumab and nivolumab.

Anlotinib+Toripalimab maintenance in Extensive-Stage small cell lung Cancer: Clinical efficacy and preclinical mechanism of anlotinib-induced neuroendocrine differentiation Suppression via Notch1.

A rationally designed bispecific antibody targeting GPC3 and PD-L1 induces tumor-directed immune activation and cytotoxicity.

Anaplastic lymphoma kinase (ALK) plays important roles in tumorigenesis and is involved in tumor immunogenicity through various pathways. Here, we conducted a comprehensive bioinformatic and clinical analysis on the characteristics of pan-cancer ALK mutation and its association with tumor immunity and the efficacy of immune checkpoint blockade. In 2930 patients with 11 tumor types treated with immune checkpoint inhibitors, the mutation of ALK indicated favorable overall survival (hazard ratio = 0.69; 95% confidence interval, 0.57-0.83; p < 0.001). We further developed and validated a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy. Moreover, multi-omics analysis on both intrinsic and extrinsic immune landscapes revealed that the mutation of ALK could enrich infiltration of immune cells, enhance tumor immunogenicity, and improve immune responses. In conclusion, ALK mutation is associated with promoted cancer immunity and can be treated as a biomarker for favorable outcomes in pan-cancer immune checkpoint blockade. These results have implications for treatment decision-making and developing immunotherapy for personalized care.

B7-H3 (CD276) is an immune checkpoint co-signaling molecule expressed on immune and non-immune cells. It is best known for suppressing T-cell responses but can also promote inflammation depending on the microenvironment. In neuroinflammatory models such as experimental autoimmune encephalomyelitis, B7-H3 expression increases concomitantly with the inflammatory response, and its inhibition is associated with reduced disease progression. Although its role in ischemic stroke remains unclear, we hypothesized that cerebral ischemia/reperfusion (I/R) would upregulate B7-H3 expression in the ischemic brain and that increased B7-H3 expression would positively correlate with pro-inflammatory cytokine expression. Young and aged male and female rodents, including normotensive and spontaneously hypertensive rats to model comorbid hypertension, underwent transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Brain tissue was collected on post-MCAO days 1, 3, 5, or 7. B7-H3 mRNA was analyzed by real-time PCR, whereas protein expression was assessed by Western blotting and immunohistochemistry at selected time points. B7-H3 expression was significantly upregulated in the ischemic brain across sexes, age groups, and species. The extent of B7-H3 degradation was influenced by species, sex, age, and time after cerebral I/R. Upregulation of B7-H3 was observed at both the mRNA and protein levels and was localized primarily to the somatosensory cortex and caudate putamen in the ipsilateral (ischemic) hemisphere, the main regions affected in this MCAO model. Elevated B7-H3 expression in the ischemic brain positively correlated with the pro-inflammatory mediator TNFα. In rats, the temporal profile of B7-H3 expression paralleled the early inflammatory phase associated with secondary tissue damage after ischemic stroke. These findings identify B7-H3 as an ischemia-induced immune checkpoint molecule in the brain that may modulate post-stroke immune responses and support further investigation into its beneficial versus detrimental roles in neuroinflammation and its potential as a therapeutic target following cerebral I/R.

Immune checkpoint targeted drug conjugate therapies: Bridging preclinical and clinical innovation for solid tumor therapy.

Globally, third leading cause of cancer-related deaths is contributed by Hepatocellular carcinoma (HCC). Chronic hepatitis B virus infection is one of the seminal etiological drivers of HCC. Hepatitis B viral DNA integration, host genomic instability, persistent inflammatory responses and the oncogenic activity of the viral oncoprotein Hepatitis B virus X (HBx), contribute to the hepatocarcinogenesis. Emerging evidences indicate that epigenetic dysregulation plays a seminal role in linking viral persistence in the liver tissue to its malignant transformation. In HBV-infected hepatocytes, aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs reprogram transcriptional networks that activate oncogenic pathways, promote proliferative signaling, and sustain cancer stem cell-like phenotypes driving HCC progression. The epigenetic modifications in the infected, malignant hepatic cells can influence the tumor microenvironment, contributing to the infiltration of exhausted cytotoxic T lymphocytes with elevated PD-1 and Tim-3 expression. Further, the T lymphocytes exhibit reduced proliferative capacity, impaired cytokine secretion, and diminished cytotoxic activity. In the clinical perspective, long-term nucleotide analogue therapy causes viral suppression and attenuation of inflammation, thereby reducing HCC progression by 40-80%. Despite the extensive T-cell exhaustion, HBV-associated HCC (HBV-HCC) is responsive to immune checkpoint blockade, as highlighted in the CheckMate-040 trial. Emerging therapeutic strategies combine anti-viral agents with immune checkpoint inhibitors, epi-drugs and HBsAg-directed TCR-engineered T cells. These clinical approaches aim to simultaneously restore antitumor immune responses as well as neutralize the viral oncogenic drivers, offering promising avenues for improved management of HBV-induced HCC.

C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.

Pneumonitis risk from pembrolizumab in non-small cell lung cancer: Interstitial abnormalities matter, and so does treatment.

Diagnosis of immune checkpoint inhibitor-related myocarditis (ICI-M) represents a substantial challenge in clinical practice. A range of imaging and laboratory parameters are frequently utilized for diagnosis, but the reliability of these modalities remains controversial. The present meta-analysis evaluates diagnostic and prognostic parameters in ICI-M. After screening PubMed, Cochrane, and Wiley Library, data from 29 trials with 3568 patients were included. In ICI-M, abnormal cardiac magnetic resonance imaging (CMR) was present in 63.4%, including late gadolinium enhancement (LGE) in 65.3% (odds ratio (OR) 5.32, 95% confidence interval (CI) 1.61-17.50; n = 424; p = 0.006) and myo- or pericardial oedema in 16.4% (OR 4.79, 95% CI 0.96-23.92; n = 145; p = 0.06). The most common LGE pattern was mid-myocardial (43%) distribution. Decreased left ventricular ejection fraction (LVEF) was present in 35.9% (OR 5.22, 95% CI 2.02-8.42; n = 1319; p = 0.001) of transthoracic echocardiography (TTE). Cardiac troponins (cTn) (standardized mean difference (SMD) 0.79, 95% CI 0.14-1.44; n = 323; p = 0.02) and brain natriuretic peptides (SMD 0.92, 95% CI 0.30-1.54; n = 201; p = 0.003) were increased in ICI-M. Reduced LVEF (OR 5.11, 95% CI 2.53-7.68; n = 222; p < 0.001) and cTnI elevation (SMD 2.27, 95% CI 0.33-4.22; n = 76; p = 0.02) predicted major adverse cardiovascular events. The study was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD420251087222). Distinct CMR-, TTE-, and laboratory parameters were associated with ICI-M, but did not serve as standalone diagnostic criterium. Aggregate data emphasize the heterogeneity of ICI-M, underscoring the necessity for a multimodal diagnostic approach.

The prognosis for patients with esophageal squamous cell carcinoma (ESCC) is poor, mainly due to the immunosuppressive tumor microenvironment (TME). However, the underlying mechanism and strategies to reverse this immunosuppressive TME remain to be clarified. This study aimed to identify key factors contributing to ESCC immunosuppressive TME, to investigate the regulatory role of diosmetin (DIOS), and to explore its potential in enhancing the anti-PD-1 therapy efficacy. Bioinformatics analysis identified the key factors affecting the ESCC immune microenvironment. Cell proliferation, transwell migration, invasion, tube formation, spheroid sprouting and Chick chorioallantoic membrane (CAM) assays evaluated the effect of DIOS on angiogenesis. Transcriptomic sequencing clarified the mechanism of DIOS in ESCC cells and HUVECs. Molecular docking, Cellular thermal shift assay (CETSA), pull down and Surface plasmon resonance (SPR) assays detected the binding of DIOS to target proteins. Finally, the combined effect of DIOS and anti-PD-1 antibody was explored in vivo. Angiogenesis and CD8+T cell suppression were key contributors to ESCC immunosuppression. DIOS suppressed angiogenesis in ESCC cells via the AURKB/AKT/STAT4/PDGFC axis and in HUVECs stimulated by ESCC CM via the JAK1/STAT1/PDGFC pathway. Clinically, high PDGFC was associated with poor prognosis and limited immune checkpoint blockade efficacy in ESCC patients. Meanwhile, DIOS promoted both T cell adhesion and migration, as well as the killing capacity of CD8⁺T cells. Furthermore, anti-CD8 antibody attenuated the anti-tumor effect of DIOS. Notably, the combination of DIOS with anti-PD-1 antibody inhibited the growth of ESCC without causing significant kidney toxicity. This study demonstrates for the first time that the natural compound DIOS dually suppresses tumor angiogenesis and enhances CD8⁺T cell function. And the combination of DIOS with anti-PD-1 antibody enhanced anti-tumor efficacy in ESCC. These findings provide a novel strategy for developing low-toxicity immunotherapy combinations based on natural products.

Ubiquitination is a critical post-translational modification that regulates protein stability, signalling pathways, and cellular homoeostasis. Increasing evidence shows that oncogenic viruses exploit the host ubiquitin system to promote viral persistence, immune evasion, and malignant transformation. Among the various host factors targeted, deubiquitinating enzymes (DUBs) play a pivotal role because they reverse ubiquitination, thereby regulating the stability, localization, and activity of key signalling proteins. Ubiquitin-specific peptidase 10 (USP10) has emerged as a particularly critical DUB in the context of viral tumourigenesis, functioning as a molecular rheostat that balances tumour suppression and oncogenic progression. The dysregulation of USP10 by viral oncoproteins facilitates a dual assault on the host: the subversion of innate immune sensors, specifically the RIG-I, MAVS, and cGAS-STING pathways, and the evasion of adaptive immune surveillance through the stabilisation of immune checkpoints, such as PD-L1, and the disruption of MHC-I antigen presentation. This comprehensive analysis explores the biochemical architecture of USP10, its paradoxical roles in cancer, and the specific mechanisms through which oncogenic viruses exploit this enzyme to drive malignancy and immune escape.

Steroid-induced modulation of the tumor immune microenvironment: Implications for cancer progression and immunotherapy outcomes.

DysUFMylation reprograms immunosuppressive neutrophils to potentiate anti-PD-1 therapy in hepatocellular carcinoma.

EGFR and IRE1α pathways are associated with distinct immunomodulatory gene expression profiles in NSCLC cells with acquired resistance to EGFR TKIs.

RNF26 regulating tumor immunogenicity of hepatocellular carcinoma by degrading GRP78 and instigating ER stress.

Combination therapy with immune checkpoint inhibitors (ICIs) has become a standard treatment for metastatic renal cell carcinoma (mRCC). However, ICIs may also cause immune-related adverse events. We report a case of mRCC that developed fulminant immune-related enterocolitis. A 79-year-old man received ICIs therapy for mRCC and was urgently hospitalized because of worsening diarrhea. Despite the initiation of steroid therapy, circumferential intestinal necrosis developed, necessitating subtotal colectomy. The patient subsequently developed cytomegalovirus- and Epstein-Barr virus-associated enterocolitis and died from extensive intestinal necrosis caused by severe thrombosis secondary to disseminated intravascular coagulation. Persistent diarrhea during ICIs therapy requires prompt evaluation and specialist consultation, even when symptoms appear mild, as they may signal immune-related enterocolitis. Clinicians should also remain vigilant for infectious complications, which can exacerbate the severity of immune-related enterocolitis and lead to life-threatening outcomes.

Circulating proteomic markers are associated with measures of small and large fiber neuropathy and symptoms in type 2 diabetes.

Survival trends among patients with newly diagnosed stage IVB cervical cancer before and after the approval of bevacizumab and immunotherapy.

Cardiovascular disease is a leading cause of morbidity and mortality among patients with cancer, yet individual risk is highly heterogeneous. This review examines cardiometabolic vulnerability as a unifying framework linking baseline cardiometabolic risk factors with cancer therapy-related cardiovascular injury and discusses emerging pharmacologic and lifestyle interventions for cardiovascular risk mitigation. Epidemiologic and mechanistic studies demonstrate that obesity, insulin resistance, dyslipidemia, and hypertension, often exacerbated by cancer therapies, amplify systemic inflammation, neurohormonal activation, endothelial dysfunction, and metabolic inflexibility. These disturbances interact with specific anticancer treatments, including anthracyclines, HER2-targeted agents, VEGF pathway inhibitors, endocrine therapies, and immune checkpoint inhibitors, increasing susceptibility to diverse cardiovascular toxicities. Emerging evidence supports multimodal preventive strategies integrating pharmacologic interventions targeting neurohormonal, metabolic, and inflammatory pathways with lifestyle modifications, though optimal approaches require further validation in cancer populations. Cardiometabolic vulnerability provides a framework to understand heterogeneous cardiovascular risk in cancer patients. Integrating cardiometabolic profiling with therapy-specific risk assessment may improve prevention strategies in cardio-oncology. Continued research is needed to refine risk stratification and inform personalized approaches for this growing population.