Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy

Background
Metastatic melanoma resistant to immune checkpoint inhibitors remains difficult to treat, and while adoptive tumor-infiltrating lymphocyte (TIL) therapy has shown durable responses, its reliance on lymphodepleting chemotherapy and high-dose…

Dihydropyrimidine dehydrogenase modulates immune response to checkpoint inhibition in mismatch repair deficient/microsatellite instability-high colorectal cancer

Background
Treatment with immune checkpoint inhibitors (ICIs) has radically improved outcomes for patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Intrinsic and acquired resistance, however, remains an importa…

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…

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