The temporal progression of lung immune remodeling during breast cancer metastasis.

Tumor metastasis requires systemic remodeling of distant organ microenvironments that impacts immune cell phenotypes, population structure, and intercellular communication. However, our understanding of immune phenotypic dynamics in the metastatic niche remains incomplete. Here, we longitudinally assayed lung immune transcriptional profiles in the polyomavirus middle T antigen (PyMT) and 4T1 metastatic breast cancer models from primary tumorigenesis, through pre-metastatic niche formation, to the final stages of metastatic outgrowth at single-cell resolution.

Temporal genomic analysis of melanoma rejection identifies regulators of tumor immune evasion.

Decreased intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogenous tumors may display variability in their aggressiveness, and how immunologic-factors impinge on their aggressiveness remains understudied. Here we studied the mechanisms responsible for the immune-escape of murine tumors with low ITH.

Clonal hematopoiesis is associated with protection from Alzheimer's disease.

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD.

interactions in the locus regulate stage-dependent enhancer activation.

Individual elements within a superenhancer can act in a cooperative or temporal manner, but the underlying mechanisms remain obscure. We recently identified an superenhancer, within which different elements act at distinct stages of type 1 classical dendritic cell (cDC1) development. The +41-kb enhancer is required for pre-cDC1 specification, while the +32-kb enhancer acts to support subsequent cDC1 maturation.

Repertoire Remodeling through CD4 T-cell Depletion.

Understanding the cellular regulation of tumor-specific CD8 T-cell responses is critical to designing improved clinical strategies for cancer immunotherapy. In this issue, Aoki and colleagues deepen our knowledge of this topic by demonstrating that transient depletion of CD4 T cells in patients with gastrointestinal cancer induces remodeling of the T-cell repertoire, including clonal replacement and expansion of CD8 T-cell clones shared between the blood and tumor..

Opposing T cell responses in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis is a model for multiple sclerosis. Here we show that induction generates successive waves of clonally expanded CD4, CD8 and γδ T cells in the blood and central nervous system, similar to gluten-challenge studies of patients with coeliac disease. We also find major expansions of CD8 T cells in patients with multiple sclerosis.