Single-cell and spatial transcriptomics reveal that the CXCL12-CXCR4 axis drives the immune-desert phenotype in small cell lung cancer by recruiting immunosuppressive CXCR4+ neutrophils and S100A8+ monocytes

Background
Small cell lung cancer (SCLC) is a recalcitrant malignancy with limited responses to immunotherapy, largely due to its uniquely immunosuppressive tumor microenvironment (TME). However, the molecular mechanisms driving this phenotype remain …

Regional immunosuppression and associated systemic markers in focally relapsed sarcomatoid mesothelioma: case report

A 52-year-old man presented with sarcomatoid diffuse pleural mesothelioma that had relapsed at an isolated site after a complete response to dual-immune checkpoint inhibition (ICI). Targeted sequencing exhibited amplification of chromosome 9p24, encom…

Precision modeling of tumor antigen-specific T-cell responses in humanized mice for preclinical assessment of cancer immunotherapies

Background
Humanized mice are highly valuable models for the preclinical development of cancer immunotherapies. However, conventional models often fail to mount robust and trackable tumor antigen-specific (TA-specific) T-cell responses, which hinders …

Non-enzymatic Rnaseh2c orchestrates proliferating macrophage-driven immunosuppression and HCC progression via Cdk9 proliferation axis and CCL2/CCR2-mediated CD8+ Tex infiltration: a novel therapeutic paradigm with “Rnaseh2c-In1” inhibitor

Background
Tumor-associated macrophages are pivotal drivers of hepatocellular carcinoma (HCC) progression. However, the functional contributions of proliferating macrophages (Prolif Ms) within the tumor microenvironment (TME) remain poorly defined.

M…

Comprehensive molecular characterization of cfDNA as predictive and monitoring biomarkers in advanced gastric cancer receiving immunotherapy

Background
Advanced gastric cancer (aGC) exhibits substantial heterogeneity in response to combination immunotherapy. Circulating cell-free DNA (cfDNA) enables non-invasive profiling of tumor dynamics and may provide biomarkers for response prediction…

Toward organ preservation in thoracic malignancies: why interpretable multimodal radiopathomics matters in the neoadjuvant immunotherapy era

Neoadjuvant immunotherapy has increased rates of pathological complete response (pCR) in thoracic malignancies and has renewed interest in organ-preserving strategies. In esophageal squamous cell carcinoma (ESCC), the Surgery As Needed for Oesophageal…

Data-informed optimization of CAR T-cell therapy long-term follow-up

Following administration of chimeric antigen receptor (CAR) T-cell therapy, extensive long-term follow-up (LTFU) requirements and complex data collection processes have posed significant challenges for patients and providers. To reassess whether a 15-…

Stem-like PD-1+TCF-1+ CD8+ T cells result from helpless priming and rely on CD4+ T-cell help to complete their cytotoxic effector differentiation

Background
Antigen-specific CD8+ T cells can be in a stem-like programmed cell death protein-1 (PD-1)+TCF-1+ differentiation state that progresses into terminal exhaustion in cancer and chronic infection. These stem-like cells are important, since the…

Gut-targeted strategies at the intersection of radiotherapy and immunotherapy

The gut microbiota has emerged as a critical determinant of therapeutic immunity, shaping responses to immune checkpoint inhibitors, adoptive cellular therapies, and radiotherapy (RT). Interest has grown in whether interventions targeting the microbio…

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