Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer

Background
Novel therapies to prevent lethal castration-resistant prostate cancer in response to standard-of-care androgen deprivation therapy (ADT) are required. Unfortunately, most prostate cancers are “immune cold” and fail to respond to checkpoint…

NKG2A-HLA-E axis contributes to an immunosuppressive checkpoint network in hepatocellular carcinoma

Background
The immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) limits the efficacy of current immunotherapies. The interplay between the emerging inhibitory receptor NKG2A and its activating counterpart NKG2C, both binding H…

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 …

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…

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 …

HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC

Background
Non-small cell lung cancer (NSCLC) is one of the frequently occurring cancers characterized by molecular heterogeneity and multiple immune cell infiltration patterns, which are associated with treatment sensitivity and resistance. However, …

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…

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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