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Abstract The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5 + ) in their native in vivo state, we find an expanded pool of Lgr5 + cells in NMRs, and these cells specifically at the crypt base (Lgr5 +CBC ) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5 +CBC cells. Instead of entering quiescence (G0), NMR Lgr5 +CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

Abstract The level of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative (TNBC) and HER2-positive breast cancers convey prognostic information. The importance of systemic immunity to local immunity is unknown in breast cancer. We previously demonstrated that histological alterations in axillary lymph nodes (LNs) carry clinical relevance. Here, we capture local immune responses by scoring TILs at the primary tumor and systemic immune responses by recording the formation of secondary follicles, also known as germinal centers, in 2,857 cancer-free and involved axillary LNs on haematoxylin and eosin (H&E) stained sections from a retrospective cohort of 161 LN-positive triple-negative and HER2-positive breast cancer patients. Our data demonstrate that the number of germinal center formations across all cancer-free LNs, similar to high levels of TILs, is associated with a good prognosis in low TILs TNBC. This highlights the importance of assessing both primary and LN immune responses for prognostication and for future breast cancer research.

Necroptosis is a form of cell death characterized by membrane rupture via MLKL oligomerization, although mechanistic details remain unclear. Here, the authors show that MLKL ubiquitylation of K219 facilitates high-order membrane assembly and subsequent rupture, promoting cytotoxicity.

Triple negative breast cancers harbor multiple copy number aberrations driving gene expression changes thought to underpin their malignant phenotypes. Here the authors integrate these features, finding and functionally validating 37 gene addictions among which they identify the mechanism of addiction to KIFC1, a potential selective drug target.

Adoptive transfer of chimeric antigen receptor (CAR) T cells has shown promising anticancer results in clinical trials. Here the authors use the human sodium iodide symporter (hNIS) as a reporter gene to image human CAR T cells in cancer-bearing mice using broadly available tracers and imaging platforms.