Evaluating the potential of candidate surrogate endpoints for overall survival in treatment-naive metastatic melanoma treated with anti-PD-1-based regimens with or without anti-CTLA-4 therapy

Background
Using surrogates for overall survival (OS) may expedite the development of, and patient access to, novel treatments. We assessed potential surrogates for OS in patients with metastatic melanoma treated with nivolumab-containing regimens in …

Spatial habitat radiomics predicts tertiary lymphoid structure status and identifies an IDO1+ migratory dendritic cell axis in breast cancer

Background
Tertiary lymphoid structures (TLS) are spatially organized immune niches associated with therapeutic response and favorable outcomes in breast cancer (BC). However, TLS assessment currently relies on invasive tissue-based analyses, and the …

GTPase RAB31 supports ANXA1-driven macrophage education through clathrin-mediated endocytosis to suppress antitumor immunity

Background
Tumor-associated macrophages (TAMs) play pivotal roles in shaping the tumor-microenvironment (TME) through functional plasticity, which is regulated by extrinsic and intrinsic signals. However, the role of vesicular trafficking in TAMs rema…

Overall survival of immunotherapy versus standard of care in chemorefractory microsatellite stable metastatic colorectal cancer: a propensity score matched analysis of 708 patients

Background
Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). However, selected patients with specific metastatic patterns may derive benefit.

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Targeting the PD-L1-induced PDK4/GLS metabolic axis overcomes anti-PD-1 resistance in non-small cell lung cancer

Background
Metabolic reprogramming within the tumor microenvironment is a pivotal barrier to effective immune checkpoint blockade (ICB). While programmed death ligand 1 (PD-L1) is well characterized as a ligand inhibiting T-cell function, its intrinsi…

LIM and SH3 protein 1 deficiency confers resistance to cytotoxic lymphocyte-mediated lysis and immunotherapy in gastric cancer by disrupting cytoskeleton dynamics

Background
A substantial amount of research has been dedicated to the mechanisms by which tumor cells evade immune system recognition and manipulate the immune microenvironment to facilitate immune escape. Recent studies have shown that viruses and tu…

Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates efficacy

Background
Antibody-drug conjugates (ADCs) and bispecific antibodies represent a rapidly advancing frontier in oncology, yet the abnormal tumor microenvironment (TME) hinders their delivery and reduces efficacy. Emerging immunomodulatory ADCs (IM-ADCs…

Normal-immunopeptidome denominator: a safety atlas for immunotherapies targeting non-canonical and aberrantly expressed tumor antigens

Proteogenomic cancer antigen discovery now extends beyond somatic mutations to include unmutated, aberrantly expressed, and non-canonical sources. We distinguish two orthogonal dimensions: molecular origin (canonical or non-canonical) and normal-tissu…

Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy

Background
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with dismal outcomes, especially in relapsed/refractory settings. Chimeric antigen receptor natural killer (CAR-NK) cell therapy holds promise but is constrained by the im…

Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states

Background
High-grade serous ovarian cancer (HGSOC) is commonly accompanied by malignant ascites, a clinically relevant tumor niche that promotes immune evasion, metastasis, and treatment resistance. Although natural killer (NK)-cell dysfunction has b…

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