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…

Super-high tumor mutational burden predicts complete remission following immunotherapy: from Petos paradox to druggable cancer hallmark

Background
The somatic mutation theory predicts that cancer risk should scale proportionally with lifetime cell divisions; yet large-bodied and long-lived species exhibit lower-than-expected cancer incidence—a long-standing contradiction termed …

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…

Clinical factors influencing retreatment with anti-PD-(L)1 therapies after treatment in early-stage cancers: a modified Delphi consensus study

Anti-programmed death (ligand) 1 (anti-PD-(L)1) therapies were first introduced in the metastatic setting and have since been approved and reimbursed for treating early-stage cancers in the adjuvant, perioperative, and neoadjuvant settings in many can…

B7-H3 and CSPG4 co-targeting as Pan-CAR-T cell treatment of triple-negative breast cancer

Purpose
Chimeric antigen receptor T (CAR-T) cell therapy is under clinical investigation in patients with metastatic triple-negative breast cancer (TNBC). However, the identification of targetable antigens remains a high priority to avoid toxicity and…

Adoptively transferred macrophages for cancer immunotherapy

Background
Macrophages have been classically associated with their innate immune functions of responding to acute injury or pathogenic insult, but they have been largely overlooked as primary initiators of adaptive immune responses. Here, we demonstra…

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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