Defects in the necroptosis machinery are a cancer resistance mechanism to checkpoint inhibitor immunotherapy

Background
Immune checkpoint inhibitors (ICIs) of programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) reinvigorate strong polyclonal T-cell immune responses against tumor cells. For many patients, these ther…

Carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of patients with extensive stage small-cell lung cancer: the GOIRC-01-2019 CeLEBrATE study

Background
The addition of a programmed death-ligand 1 (PD-L1) inhibitor, either atezolizumab or durvalumab, to platinum-etoposide prolonged survival in a limited subset of patients with extensive-stage small-cell lung cancer (ES-SCLC). Preclinical st…

LILRB2 blockade facilitates macrophage repolarization and enhances T cell-mediated antitumor immunity

Background
Immune checkpoint inhibitors have revolutionized the treatment of solid tumors, enhancing clinical outcomes by releasing T cells from inhibitory effects of receptors like programmed cell death protein 1 (PD-1). Despite these advancements, a…

Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkins lymphoma

Background
Chimeric antigen receptor (CAR) T-cell therapy depends on T cells that are genetically modified to recognize and attack cancer cells. Their effectiveness thus hinges on the functionality of a patient’s own T cells. Since CAR T-cell th…

Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors

Background
Effector regulatory T cells expressing C-C chemokine receptor 4 (CCR4) suppress antitumor immune responses. We conducted a phase I clinical trial to evaluate the safety and efficacy of preoperative combination therapy with mogamulizumab (an…

Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade

Background
Immune checkpoint blockade (ICB) can induce antitumor efficacy but also induces immune-related adverse events. Systemically administered ICB can activate immune cells throughout the host. Conditionally active ICB with proteolytically cleave…

Systemic immunomodulation by irreversible electroporation versus stereotactic ablative body radiotherapy in locally advanced pancreatic cancer: the CROSSFIRE trial

Background
Irreversible electroporation (IRE) and stereotactic ablative body radiotherapy (SABR) are cytoreductive therapies for locally advanced pancreatic cancer (LAPC). Both may signify immunogenic cell death. We aimed to compare systemic immune re…

mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors

Background
Perturbation of the mechanistic target of rapamycin (mTOR) pathway can instruct effector versus memory cell fate of tumor antigen-specific T cells in preclinical models. In this study, we sought to understand the impact of rapamycin (siroli…

Cardiac MRI study of adverse events in patients treated with immune checkpoint inhibitors: a prospective cohort study of cardiac adverse events

Immune checkpoint inhibitors (ICIs) revolutionized cancer therapy, yet require management of immune-related adverse events (irAEs). Fulminant myocarditis is a rare irAE, but lower-severity cardiac events are being reported more frequently, leading to …

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