AARS1-mediated lactylation reprograms macrophage lipid metabolism to restrict antitumor immunity

Background
Tumor-derived lactate has long been regarded as a metabolic waste product. However, accumulating evidence indicates that lactate also functions as a signaling molecule that actively remodels the tumor immune microenvironment. How lactate-dr…

DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy

Background
Long-term survival of extensive-stage small-cell lung cancer (ES-SCLC) remains rare, with most patients experiencing disease progression during maintenance therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors have the potential to confer…

T cells are critical for pre-metastatic niche formation through the STAT3/IL-17 axis

Background
Pre-metastatic niches composed of mainly myeloid cells are recognized as critical for tumor metastasis. However, whether adaptive immune cells also play an important role in pre-metastatic niche formation remains to be explored.

Methods
CD…

Turning off methylglyoxal stress: an alternative approach to inhibit MDSC expansion and metastasis in triple-negative breast cancer

Background
Metabolic reprogramming through enhanced glycolysis is a hallmark of cancer that supports tumor progression and promotes protumor immune responses. Methylglyoxal (MG), a reactive by-product of glycolysis, has recently emerged as an oncometa…

Development of an immunocompetent cutaneous squamous cell carcinoma model identifies VISTA and CTLA-4 as targetable immune checkpoints

Background
Immunotherapeutic approaches for cutaneous squamous cell carcinoma (cSCC) remain limited to programmed cell death protein 1 (PD-1) blockade. Although genomics studies have characterized key driver mutations in cSCC, preclinical models that …

N-glycans in non-malignant tumor microenvironment cells dampen CAR-T cell function in solid tumors

Background
Chimeric antigen receptor (CAR) T-cell therapy has shown limited efficacy in solid tumors, largely due to immunosuppressive mechanisms within the tumor microenvironment (TME). While tumor-associated glycans are known to protect malignant ce…

PGE2-mediated NK cell reprogramming drives acquired immunotherapy resistance in lung adenocarcinoma

Background
Acquired resistance limits the durability of programmed cell death protein-1 (PD-1) blockade in lung adenocarcinoma, yet the tumor-intrinsic programs and immune circuits that drive acquired resistance relapse remain poorly defined. The purp…

Phase I safety, efficacy, and biomarker response evaluations of three oral PD-L1 inhibitors: INCB086550, INCB099280, and INCB099318

Background
Orally administered small-molecule programmed death ligand 1 (PD-L1) inhibitors may have the potential to improve patient outcomes in the treatment of a range of cancers compared with their antibody-based counterparts. A small molecule migh…

Rethinking Phase I units in the era of immuno-oncology: a three-layer framework

The rapid expansion of immuno-oncology (I-O) and other advanced therapies is reshaping the complexity of early-phase clinical development. While core Phase I principles remain fundamental across oncology, emerging modalities introduce additional requi…

Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy

Background
Nearly half of patients with melanoma do not respond to immune checkpoint inhibitors (CPIs) and many develop immune-related adverse events (irAEs), often forcing treatment discontinuation, and underscoring the need to predict and monitor ou…

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