Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors.

Neoadjuvant immunotherapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA4) + anti-programmed cell death protein 1 (PD1) monoclonal antibodies has demonstrated remarkable pathological responses and relapse-free survival in ~80% of patients with clinically detectable stage III melanoma. However, about 20% of the treated patients do not respond. In pretreatment biopsies of patients with melanoma, we found that resistance to neoadjuvant CTLA4 + PD1 blockade was associated with a low CD4/interleukin-2 (IL-2) gene signature.

Concomitant or delayed anti-TNF differentially impact on immune-related adverse events and antitumor efficacy after anti-CD40 therapy.

Background: Concomitant tumor necrosis factor (TNF) neutralization in combination with immune checkpoint inhibitors (ICIs) reduces clinical immune-related adverse events (irAEs) and appears to improve antitumor efficacy in preclinical tumor models. Agonistic antibodies targeting costimulatory receptors such as CD40 represent an additional strategy to boost antitumor immune response and potentiate the activity of ICIs. However, the dose-limiting toxicities observed in anti-CD40-treated cancer patients have hindered its clinical development.

Clinical Insignficance of Monoclonal T-Cell Populations and Duodenal Intraepithelial T-Cell Phenotypes in Celiac and Nonceliac Patients.

Refractory celiac disease (RCD) is a rare condition, usually managed at specialized centers. However, gastroenterologists and pathologists in general practices are often the first to consider a diagnosis of RCD in celiac patients with persistent symptoms. The distinction between type I and type II RCD is crucial as patients with RCD II have a shortened life expectancy.