Targeting non-canonical antigens unlocks functional T-cell responses in renal cell carcinoma

Background
Renal cell carcinoma (RCC) frequently exhibits favorable responses to immunotherapy, despite a low tumor mutational burden, suggesting a critical role for non-mutational antigens presented by human leukocyte antigen class I in activating CD…

Spatial immune atlas of breast cancer brain metastasis reveals CD163+ macrophage reprogramming associated with immune escape

Background
Brain metastases (BrM) remain a major cause of mortality in breast cancer (BC), yet the spatial organization and molecular circuitry of the metastatic immune microenvironment are poorly defined.

Methods
To address this gap, we integrated h…

Immune checkpoint inhibitor neurotoxicity: long-term outcomes with focus on 1-year neurological sequelae

Background
Data on the long-term course of neurological immune-related adverse events (n-irAEs) are limited by the size of studies as well as short and heterogeneous follow-up durations. Herein, we assessed the risk and predictors of 1-year neurologic…

Artificial intelligence-guided analysis of the tumor microenvironment predicts response to pembrolizumab in rare tumors

Background
Pathologic tumor response and changes in the tumor microenvironment (TME) predict outcomes to immune checkpoint inhibitors, but are understudied in rare tumors. We investigated whether artificial intelligence (AI)-powered analyses of pretre…

Blood-based kinase activity profiling to predict response to immune checkpoint inhibitors in patients with advanced stage NSCLC: the prospective IOpener study

Background
The programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) is used as a biomarker to predict benefit from immune checkpoint blockade (ICB) in patients with non-small cell lung cancer (NSCLC). However, additional biomarkers are neede…

VEGF-A blockade overcomes liver metastases resistance to chemoimmunotherapy in patients with advanced non-squamous NSCLC

Purpose
Liver metastases (LMs) confer resistance to immune checkpoint blockade in advanced non-squamous non-small cell lung cancer (ns-NSCLC), likely through an immunosuppressive tumor microenvironment (TME). We hypothesized that vascular endothelial …

Immunoglobulin GM ({gamma} marker) allotypes expressed on IgG1 as potential genetic markers of response to immune checkpoint blockade therapy

The results of a recent comprehensive investigation—confirmed in multiple cohorts—show that patients with hepatocellular carcinoma, who favorably responded to anti-programmed cell death protein 1 (PD-1) therapy, were enriched in IgG1-produ…

C92, a proton channel-blocking allosteric STING agonist generates robust antitumor activity

Background
The activation of stimulator of interferon genes (STING) for the treatment of cancer is a long-standing therapeutic goal. However, the clinical use of orthosteric STING agonists has shown limited utility in patients with advanced/metastatic…

From M7824 to SHR-1701: lessons for dual PD-L1/TGF-{beta} targeting

Retlirafusp alfa (SHR-1701), a bifunctional programmed death-ligand 1 (PD-L1) antibody fused to a TGF-β trap, was approved in China on January 7, 2026 for first-line treatment of PD-L1-positive advanced gastric or gastroesophageal junction adenoc…

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