Anti-PD-1 amplifies costimulation in melanoma-infiltrating T1-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, leading to durable tumor remissions. However, 55% of patients with melanoma do not respond to treatment.

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.

GDNF family receptor alpha-like (GFRAL) expression is restricted to the caudal brainstem.

Objective: Growth differentiation factor 15 (GDF15) acts on the receptor dimer of GDNF family receptor alpha-like (GFRAL) and Rearranged during transfection (RET). While Gfral-expressing cells are known to be present in the area postrema and nucleus of the solitary tract (AP/NTS) located in the brainstem, the presence of Gfral-expressing cells in other sites within the central nervous system and peripheral tissues is not been fully addressed. Our objective was to thoroughly investigate whether GFRAL is expressed in peripheral tissues and in brain sites different from the brainstem.

Multivariate analyses and machine learning link sex and age with antibody responses to SARS-CoV-2 and vaccination.

Prevention of negative COVID-19 infection outcomes is associated with the quality of antibody responses, whose variance by age and sex is poorly understood. Network approaches identified sex and age effects in antibody responses and neutralization potential of infection and vaccination throughout the COVID-19 pandemic. Neutralization values followed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific receptor binding immunoglobulin G (RIgG), spike immunoglobulin G (SIgG) and spike and receptor immunoglobulin G (S, and RIgA) levels based on COVID-19 status.