Decidual stromal cells (DSCs) are involved in immunoregulatory mechanisms that prevent fetal rejection by the mammalian maternal immune system. Recent studies using single-cell RNA sequencing demonstrated the existence of different types of human and mouse DSCs, highlighting corresponding differentiation (decidualization) pathways, and suggesting their involvement in the immune response during normal and pathological pregnancy. DSCs may be considered tissue-specialized fibroblasts because both DSCs and fibroblasts share phenotypic and functional similarities in immunologically challenged tissues, especially in terms of their immune functions. Indeed, fibroblasts can setup, support, and suppress immune responses and these functions are also performed by DSCs. Moreover, fibroblasts and DSCs can induce ectopic foci as tertiary lymphoid structures (TLSs), and endometriosis, respectively. Thus, understanding DSC immunoregulatory functions is of timely relevance.

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.