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"Hao et al. identify PTEN deficiency as a biomarker for ATR inhibition. They report that PTEN deficiency enhances sensitivity to ATR inhibitor–based therapies in preclinical models and is associated with clinical benefit in trials of high-grade serous ovarian cancer. Image credit: David A. Litman/Shutterstock."

"Peter J. Pitts, Judea Pearl, Arthur L. Caplan, Robert Goldberg"

"Synergizing radiotherapy (RT) with immune checkpoint inhibitors has emerged as a promising strategy for solid tumors. RT acts as a potent immunomodulator, capable of functioning as an in situ vaccine through the induction of immunogenic cell death and activation of innate immune sensing, thereby promoting DC maturation and CD8+ T cell responses. However, RT also triggers counter-regulatory immunosuppression, including PD-L1 upregulation and the recruitment of suppressive cells, providing the biological rationale for synergy. Here, we systematically review advances in radioimmunotherapy, covering immunomodulatory mechanisms, clinical optimization of dose and sequencing, and the emerging role of artificial intelligence (AI) in guiding treatment paradigms. We adopt a spatial interaction–centric perspective to synthesize current knowledge on how RT governs the DC/CD8+ T cell interaction axis across the tumor microenvironment and tumor-draining lymph nodes, aiming to chart a rational course from empirical combination toward personalized, precision radioimmunotherapy. Furthermore, we explore how AI-driven analysis of radiomics and multiomics data is being applied to predict responders and personalize treatment planning."

"Heart transplantation remains the gold standard therapy for patients with end-stage heart failure. However, post-transplant complications are considerable. Emerging evidence implicates the gut microbiome as a modifiable determinant of post–heart transplant outcomes through its influence on host immunity, metabolism, and inflammation. This Review synthesizes current understanding of gut microbiome dysregulation following solid organ transplantation, with particular emphasis on heart transplantation, examining mechanistic links underpinning important complications including allograft rejection, infection, metabolic dysfunction, and cardiac allograft vasculopathy. We critically evaluate bidirectional interactions between the gut microbiome and immunosuppressive drugs, assess the potential for microbiome profiling to serve as a predictive biomarker for post-transplant complications, and examine microbiome-targeted interventions including dietary modification, prebiotics, probiotics, and fecal microbiota transplant. Finally, we propose a translational roadmap to integrate microbiome science into heart transplant care to optimize immunosuppression, predict complications, and improve long-term outcomes for heart transplant recipients."

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