Circulating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma

Background
The majority of patients with melanoma develop immune-related adverse events (irAEs), and over half do not respond to anti-PD-1 (Programmed cell death protein 1) checkpoint inhibitor (CPI) immunotherapy. Accurate predictive biomarkers for b…

Tumor-secreted galectin-3 suppresses antitumor response by inducing IL-10+ B cells

Background
Breast cancer is the leading cause of cancer-related deaths among women globally. Tumor-secreted proteins foster an immunosuppressive environment, enabling immune evasion and reducing the effectiveness of antitumor immunity. Interleukin (IL…

Differential safety profiles of durvalumab monotherapy and durvalumab in combination with tremelimumab in adult patients with advanced cancers

Background
Durvalumab (D; anti-programmed cell death ligand 1 (PD-L1)) monotherapy or in combination with tremelimumab (T; anti-cytotoxic T lymphocyte antigen-4 (CTLA-4)) have demonstrated efficacy in advanced cancers. However, higher incidences of ad…

Neovascular pruning by IDO1 inhibitors can potentiate immunogenic cytotoxicity of ischemia-targeted agents to synergistically enhance anti-PD-1 responsiveness

Background
Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1’s role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinic…

Cbl-b inhibitor NX-1607 activates MAPK/ERK signaling pathway and enhances T-cell activation

Backgroud: The E3 ubiquitin ligase casitas B lymphoma-b (Cbl-b) is pivotal in modulating immune responses by attenuating T-cell activation and cytokine production. Inhibiting Cbl-b presents a potential therapeutic strategy in immuno-oncology by enha…

Dual roles of IRE1{alpha} inhibition in reversing mitochondrial ROS-induced CD8+ T-cell senescence and exerting direct antitumor effects in multiple myeloma

Background
Multiple myeloma (MM) is characterized by the proliferation of malignant plasma cells within the bone marrow (BM) microenvironment, which significantly contributes to immune suppression of CD8+ T cells. Our previous research identified that…

IL-1{beta} blockade prevents cardiotoxicity and improves the efficacy of immune checkpoint blockers and chemotherapy against pancreatic cancer in mice with obesity

Background
Immune checkpoint blockers (ICBs) have revolutionized cancer therapy, yet they remain largely ineffective in treating pancreatic ductal adenocarcinoma (PDAC). Moreover, ICBs can cause severe immune-related adverse events (irAEs), including …

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