Phase 1 study of KHK2455, a long-acting, potent and selective IDO1 inhibitor, in combination with avelumab in patients with locally advanced or metastatic urothelial carcinoma

Background
Dual inhibition of indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) may alleviate suppression of antitumor immune responses by overcoming redundant immunosuppressive pathways. This study evaluated the combination o…

Frailty of older patients is not reflected in the melanoma tumor microenvironment and treatment response to immune checkpoint blockade therapy

Older adults with frailty demonstrate systemic immunosenescence, including T-cell exhaustion and reduced immune diversity, yet maintain immune checkpoint blockade (ICB) efficacy comparable to that of younger patients. Baseline immune cell composition …

CD28-ICOS costimulation enhances the therapeutic efficacy of L1CAM-targeted CAR-T cells against ovarian and gastric cancers

Background
Ovarian and gastric cancers are associated with poor prognosis and derive limited benefit from current therapies, highlighting the need for novel immunotherapeutic approaches. The L1 cell adhesion molecule (L1CAM) is aberrantly expressed in…

CT-based deep foundation model for predicting immune checkpoint inhibitor-induced pneumonitis risk in lung cancer

Background
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but can cause serious immune-related adverse events, with pneumonitis (ICI-P) being among the most severe. Early identification of high-risk patients before ICI initiat…

Gene regulatory elements determine efficacy of BCMA-targeted CAR-T cell products

In relapsed/refractory multiple myeloma, the approved B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cell product ciltacabtagene autoleucel (cilta-cel) shows higher response rates than idecabtagene vicleucel (ide-cel) in p…

IgM promotes antitumor immunity to a Tn-expressing solid tumor

Background
Altered O-glycosylation is a hallmark of many adenocarcinomas and is often characterized by expression of the Tn antigen. However, the role of B cells in protection against Tn-expressing solid tumors remains poorly understood.

Methods
We g…

LRIG2 suppresses NK cell-induced GSDME-mediated pyroptosis via the LAMP1-STAT3 pathway in glioma

Background
Gliomas are resistant to current therapies, and natural killer (NK) cell-based immunotherapy shows limited efficacy. Gasdermin E (GSDME)-mediated pyroptosis contributes to NK-induced tumor killing, but NK cell dysfunction in the glioma micr…

Deep learning-based CT model for non-invasive prediction of tertiary lymphoid structures in pancreatic cancer: a multicenter study with prospective validation in an immunochemotherapy cohort

Background
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Tertiary lymphoid structures (TLS) have emerged as key components of the tumor immune microenvironment, associated with improved survival and enhanced immu…

Epigenetic plus cytokine therapy induces stem-like CD8+ T-cell reservoirs and intratumoral immune niches to overcome anti-PD-1 resistance

Background
Checkpoint blockade (CPB) has limited efficacy in patients with colorectal cancer (CRC), warranting improved therapeutic strategies capable of remodeling the tumor microenvironment. Stem-like TCF1+CD8+ T cells, cytotoxic CD8+ T cells, and l…

PLP1-triggered NOT gate to address neurotoxicity risk of PSMA-targeted prostate cancer therapy

Background
On-target, off-tumor toxicity is a recurring challenge for solid tumor therapeutics targeted to antigens preferentially expressed on malignant cells. Prostate-specific membrane antigen (PSMA) is a tumor-associated antigen that is expressed …

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