Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma

Background
Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFN)-induced immune homeostatic responses in melanoma cel…

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines

Background
Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a “cold” tumor type with poor i…

CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors

Background
Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a …

PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity

Background
Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further inve…

Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway

Background
Immunosuppressive phenotype compromised immunotherapy efficacy of hepatocellular carcinoma. Tumor cells intrinsic mitochondria dynamics could pass effects on the extracellular microenvironment through mtDNA stress. PGAM5 anchors at mitochon…

Targeting the NLRP3 inflammasome abrogates cardiotoxicity of immune checkpoint blockers

Background
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many malignant tumors. However, ICI-induced hyper-immune activation causes cardiotoxicity. Traditional treatments such as glucocorticoids and immunosuppressants have l…

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…

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