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…

Dexamethasone activates anti-tumor immunity in multiple myeloma by dismantling the GR-PPP1CB complex to restore STING/IRF3 signaling

Background
The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) pathway mediates anti-tumor immunity by sensing cytosolic DNA and producing type I interferons, but is frequently suppressed in multiple myeloma (MM), enabling immune e…

Rescue by radiotherapy and anti-CTLA4/PD-1 after failure of anti-PD-1 therapy in patients with metastatic NSCLC: the phase II RECLAIM trial

Background
Response to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy remains limited in patients with metastatic non-small cell lung cancer (NSCLC), whose tumors exhibit low or absent programmed death-ligand 1 (PD-L1) expression, and …

IL-10 secretion by CD8 T cells orchestrates early NK cell recruitment and antitumor immunity after anti-VEGFR-2/PD-1 therapy

Background
The combination of antiangiogenic therapy with immune checkpoint blockade has demonstrated significant clinical benefits in various cancers, however, the precise mechanisms of action on the immune system are not fully understood. In particu…

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