A cell atlas foundation model for scalable search of similar human cells.

Single-cell RNA-seq (scRNA-seq) has profiled hundreds of millions of human cells across organs, diseases, development, and perturbations to date. Mining these growing atlases could reveal cell-disease associations, discover cell states in unexpected tissue contexts, and relate in vivo biology to in vitro models. These require a common measure of cell similarity across the body and an efficient way to search.

IL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines.

One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 T cells and ~15-fold increase in the numbers of NK cells at the vaccination site.

Systematic perturbation screens identify regulators of inflammatory macrophage states and a role for TNF mRNA m6A modification.

Macrophages exhibit remarkable functional plasticity, a requirement for their central role in tissue homeostasis. During chronic inflammation, macrophages acquire sustained inflammatory 'states' that contribute to disease, but there is limited understanding of the regulatory mechanisms that drive their generation. Here we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary murine macrophages with transcriptional and cytokine profiling of genetic perturbations in primary human macrophages to uncover regulatory circuits of inflammatory states.

Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination.

Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma.

Resolving the tissue response to neoadjuvant chemotherapy in rectal cancer.

In this issue of Cell Reports Medicine, Qin et al. present a comprehensive single-cell transcriptomics analysis of the tumor microenvironment of rectal cancer tumors before and after neoadjuvant chemotherapy.