CLEC2B-KLRB1 axis acts as an immune checkpoint, governing the exhaustion of CD8+ T cells and their resistance to immune checkpoint blockade

Background
Many patients with cancer benefit little from immune checkpoint blockade (ICB), a major obstacle to immunotherapy for decades. Finding alternative immune checkpoints that control CD8+ T-cell exhaustion is urgent if we are to improve the eff…

ATF4 promotes immune evasion in oral squamous cell carcinoma by suppressing autophagic PD-L1 degradation

Background
Immune checkpoint blockade targeting programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) has revolutionized cancer therapy. However, its efficacy is frequently limited by primary and acquired resistance. While inflammatory signals tra…

Comparing immune-checkpoint inhibitor-mediated inflammatory arthritis to polymyalgia rheumatica: a prospective cohort study

Background
Immune checkpoint inhibitor (ICI)-related inflammatory arthritis occurs in approximately 6% of ICI-treated patients, and is often long-lasting. The clinical presentation is heterogeneous, and often loosely resembles either rheumatoid arthri…

FAP-CD40 and PD1-IL2v combination therapy reprograms immunologically cold tumors through de novo intratumoral T cell-dendritic cell clusters

Background
Pancreatic ductal adenocarcinoma (PDAC) remains a major challenge for immunotherapy due to its immunologically cold tumor nature, characterized by poor T cell infiltration and a highly suppressive tumor microenvironment. Here, we propose a …

Gasdermin D antagonizes immunosuppression in prostate cancer by inducing LAMC2 degradation to block M2 macrophage polarization

Background
The N-terminal domain of gasdermin D (GSDMD) is a known suppressor of prostate cancer (PCa), primarily recognized for its tumoricidal pyroptotic function. However, research on the full-length GSDMD protein and its relationship with PCa rema…

Immunotherapy for early-stage cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (CSCC) is a highly prevalent malignancy with rising incidence, particularly among elderly and immunosuppressed individuals. Although most early-stage cases are cured with surgery, a relevant minority present with high…

Phase 1/2 study of pegenzileukin, a pegylated recombinant non-alpha IL-2, with cemiplimab for the treatment of advanced unresectable or metastatic skin cancers

Background
Pegenzileukin (SAR444245), a pegylated non-alpha recombinant human interleukin (IL)-2 variant, avoids engagement of the IL-2 receptor α subunit (IL-2Rα) chain and associated toxicities, while retaining engagement of IL-2Rβ,…

Targeting VEGF signaling and stromal remodeling enhances chemoimmunotherapy efficacy in esophageal cancer

Background
Neoadjuvant chemoimmunotherapy (NACI) has shown promising results in treating esophageal squamous cell carcinoma (ESCC), yet the mechanisms driving its efficacy remain poorly defined, limiting further optimization of this regimen.

Methods

Membrane-bound TRAIL-armoring augments CAR-T cells in mesothelin-positive solid malignancies

Background
Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR)-T cell therapy shows an effective and long-lasting response in high MSLN-expressing tumors, but fails to treat tumors with heterogeneous levels of antigen expression. Here we descri…

Human CART22.19 therapy in refractory pediatric B-ALL: insights from a named-patient cohort

Background
CD19-directed chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for pediatric B-cell acute lymphoblastic leukemia (B-ALL), yet relapses driven by antigen escape remain a major limitation. Dual-targeti…

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