The adaptor protein mitochondrial antiviral signaling protein (MAVS)-mediated innate immune response is essential for host defense against RNA viruses. Gokhale and colleagues report that cellular mRNAs assemble and activate the MAVS signalosome by directly binding to MAVS and regulating its interactors, consequently enhancing antiviral signaling and interferon expression to inhibit viral infection.

Tumor-infiltrating regulatory T (TI-Treg) cells constitute key components within the tumor microenvironment (TME) to suppress antitumor immunity and facilitate tumor progression. Although multiple therapies have been developed to eliminate TI-Treg cells, most of them exhibit only modest efficacy and harbor risks of inducing immune-related adverse events (irAEs). Recent studies demonstrate that CC chemokine receptor (CCR)8 is highly and specifically expressed on effector TI-Treg cells in mice and humans, highlighting CCR8 as a promising target for selective TI-Treg cell depletion in the treatment of various cancers. Here, we concentrate on the latest understanding of CCR8 regarding its expression, functions, and regulation, and summarize the current landscape of CCR8-targeted therapies. With favorable efficacy and safety, the latter represent an important class of next-generation putative cancer immunotherapies.

Mayassi and colleagues utilized spatial transcriptomics to create a comprehensive blueprint of the mouse gut, exploring its adaptability and resilience under perturbed conditions. Their work highlights the adaptive capabilities of the murine gut’s regionalized structure, providing insights into how it functions in a coordinated manner and how it responds to external challenges.

Lim and colleagues demonstrate that synNotch transcriptional circuits engineered into T cells can be used to precisely control location-specific expression of payloads responding to antigen triggers, thus locally inhibiting unwanted immunity or neuroinflammation. With no off-tumor toxicity or systemic immunosuppression upon elimination of mouse brain tumors, this approach can achieve better efficacy than anticipated.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, characterized by multiple histological subtypes, each with distinct pathological and clinical features. Current treatment approaches include cytotoxic chemotherapies, poly(ADP-ribose) polymerase (PARP) inhibitors, bevacizumab, hormonal therapy, immunotherapy, and antibody–drug conjugates (ADCs). In this review we discuss immune evasion mechanisms in OC and the role of genetics, the tumor microenvironment, and tumor heterogeneity in influencing these processes. We also discuss the use of immunotherapies for OC treatment, either alone or in combination with other anticancer agents, with a focus on their clinical outcomes. Finally, we highlight emerging immunotherapies that have either succeeded or are on the verge of significantly impacting cancer treatment, and we discuss their potential utility in the effective treatment of OC.

Conventional dendritic cells (cDCs) are sentinels of the mammalian immune system that sense a wide range of danger and homeostatic signals to induce appropriately targeted T cell immune responses. Traditionally classified into two main subsets, cDC1 and cDC2, recent research shows that cDC2s exhibit significant heterogeneity and can be further subdivided. Studies in mice and humans show that, beyond their ontogeny, cDC2s acquire dynamic and tissue-specific characteristics that are influenced by local environmental signals, which impact on their functions during homeostasis, inflammation, and infection. The novel concept is proposed that tissue-derived signals and tissue plasticity can override preestablished developmental programming, thereby redefining developmental trajectories and cDC2 functionality. Ultimately, understanding cDC2 heterogeneity and plasticity has important implications for modulating T cell immunity in health and disease.

Community engagement is essential for shaping equitable biomedical research priorities, but it is often underutilized, especially for marginalized populations. To integrate community feedback from the public into research, herein we describe a collaborative pilot funded by the Chan Zuckerberg Initiative which pairs University of California San Francisco (UCSF) with the Rafiki Coalition for Health and Wellness. Utilizing focus groups modeled on Research Prioritization by Affected Communities, participants identified themes that included mistrust in healthcare, representation gaps, and the need for culturally responsive research. Priorities such as mental health, chronic disease, and access to black providers were highlighted. The findings emphasize the need for sustained, grassroots partnerships to drive inclusive research agendas.