Anti-PD-1 amplifies costimulation in melanoma-infiltrating Th1-like Foxp3+ regulatory T cells to alleviate local immunosuppression

Background
Immune checkpoint inhibitors targeting programmed cell death protein-1 (PD-1) are the first line of treatment for many solid tumors including melanoma. PD-1 blockade enhances the effector functions of melanoma-infiltrating CD8+ T cells, lea…

Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression

Background
The E3 ubiquitin ligase murine double minute 2 (MDM2) binds the p53 transcriptional activation domain and acts as a potent inhibitor of TP53 pathway, one of the three most crucial oncogenic pathways in urothelial carcinoma (UC). However, th…

XCL1-secreting CEA CAR-T cells enhance endogenous CD8+ T cell responses to tumor neoantigens to confer a long-term antitumor immunity

Background
Therapeutic efficacy of carcinoembryonic antigen (CEA)-specific chimeric antigen receptor (CAR) T cells against colorectal cancer (CRC) remains limited due to the unique characteristics and distinct microenvironments of tumor tissues. We mo…

Nivolumab plasma concentration and clearance associated with overall survival in patients with renal cell carcinoma

Background
Nivolumab is an immune checkpoint inhibitor (ICI) that selectively inhibits programmed cell death protein 1 activation, restoring antitumor immunity. ICIs are indicated for various types of advanced solid tumors; however, not all patients b…

Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors

Background
Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing…

GP73 reinforces cytotoxic T-cell function by regulating HIF-1{alpha} and increasing antitumor efficacy

Background
Immunotherapy that targets immune checkpoints has achieved revolutionary success, but its application in solid tumors remains limited, highlighting the need for reliable enhancement of the efficacy of immunotherapy. Golgi protein 73 (GP73),…

Novel and potent MICA/B antibody is therapeutically effective in KRAS LKB1 mutant lung cancer models

Background
Concurrent KRAS LKB1 (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could…

CREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment

Background
To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they rel…

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