Can Skills Training Prevent Relationship Problems in At-Risk Couples? Four-Year Effects of a Behavioral Relationship Education Program

Eighty-three couples were stratified into groups at high and low risk for relationship distress and randomized to either the Self-Regulatory Prevention and Relationship Enhancement Program (Self-PREP) or a control condition. As predicted, there were differential effects of Self-PREP on high-risk and low-risk couples. Because of low statistical power, results must be interpreted cautiously, but at 1-year follow-up high-risk couples in Self-PREP showed trends toward better communication than control couples. However, there was no difference in the communication of Self-PREP and control low-risk couples. High-risk couples receiving Self-PREP exhibited higher relationship satisfaction at 4 years than control couples, but in low-risk couples relationship satisfaction was higher in the control condition. High-risk couples seemed to benefit from skills-based relationship education, but low-risk couples did not

Adenosine 2A receptor blockade as an immunotherapy for treatment-refractory renal cell cancer

Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an immunotherapy, we performed a phase I clinical trial with a small-molecule A2AR antagonist. We find that this molecule can safely block adenosine signaling in vivo. In a cohort of 68 patients with renal cell cancer (RCC), we also observe clinical responses alone and in combination with an anti-PD-L1 antibody, including subjects who had progressed on PD-1/PD-L1 inhibitors. Durable clinical benefit is associated with increased recruitment of CD8+ T cells into the tumor. Treatment can also broaden the circulating T-cell repertoire. Clinical responses are associated with an adenosine-regulated gene-expression signature in pretreatment tumor biopsies. A2AR signaling, therefore, represents a targetable immune checkpoint distinct from PD-1/PD-L1 that restricts antitumor immunity. SIGNIFICANCE: This first-in-human study of an A2AR antagonist for cancer treatment establishes the safety and feasibility of targeting this pathway by demonstrating antitumor activity with single-agent and anti-PD-L1 combination therapy in patients with refractory RCC. Responding patients possess an adenosine-regulated gene-expression signature in pretreatment tumor biopsies.See related commentary by Sitkovsky, p. 16.This article is highlighted in the In This Issue feature, p. 1