Latest Research
All publications from the Cancer3.AI database, newest first.
Risk factor profiles and haemodynamic progression in aortic stenosis: a retrospective population-based study.
Lee M, et al
A large retrospective study published in Heart examined how quickly aortic stenosis — a narrowing of the heart's main outflow valve — progresses in real-world patients, and which risk factors predict the fastest deterioration. Using data from over 70,000 patients in the Kaiser Permanente Southern California health system, researchers analyzed more than 111,000 pairs of echocardiograms recorded between 2011 and 2021. They found that rapid haemodynamic progression occurred in 7.8% of patients with early valve changes, 16.4% with mild stenosis, and nearly 30% of those with moderate stenosis. Importantly, the risk factors associated with rapid progression differed by disease stage: in early disease, systemic conditions such as anaemia, obesity, liver disease, renal failure, and cancer were the strongest predictors, while in moderate stenosis, the valve measurements themselves were most informative. The findings suggest that current one-size-fits-all surveillance guidelines may miss high-risk patients, and that integrating both clinical and echocardiographic data into monitoring strategies could help clinicians identify those who need closer follow-up or earlier surgical intervention.
Heart (British Cardiac Society)
Source →An immunobiliary single-cell atlas resolves crosstalk between type 2 conventional dendritic cells and γδ T cells in cholangitis.
Thomann S, et al
Researchers created a comprehensive single-cell atlas of the liver and liver-draining lymph nodes in mice with cholestatic liver disease, a condition that mirrors human biliary disorders such as primary sclerosing cholangitis and primary biliary cholangitis. The study identified a specific subset of immune cells called Mgl2+ type 2 conventional dendritic cells (cDC2B) that accumulate around bile ducts during liver injury and actively communicate with gamma-delta T cells to drive inflammation. This communication relies on a direct cell-to-cell contact signal involving the Icosl-Icos molecular pair, and when cDC2B cells were experimentally depleted, the inflammatory gamma-delta T cell response was significantly reduced. The gamma-delta T cells promote liver fibrosis — the dangerous scarring process that can lead to cirrhosis — through the cytokine IL-17, and mice lacking IL-17 or depleted of gamma-delta T cells showed markedly less fibrosis. These findings reveal a previously unrecognized immune circuit in the biliary niche and highlight cDC2B cells and the IL-17 pathway as potential therapeutic targets for patients suffering from chronic cholestatic liver diseases.
Nature communications
Source →Unveiling alternate pathways for SARS-CoV-2 infection via extracellular vesicle-mediated transfer of ACE2 and TMPRSS2.
Rea-Moreno M, et al
Researchers investigated how SARS-CoV-2, the virus responsible for COVID-19, manages to infect a wide variety of lung cells beyond those that naturally carry its known entry proteins, ACE2 and TMPRSS2. The study found that in human lung epithelial cells, TMPRSS2 is not primarily located on the cell surface as previously believed, but resides inside the cell and is packaged together with ACE2 into tiny membrane-enclosed particles called extracellular vesicles (EVs). These EVs are released by lung epithelial cells and taken up by neighboring cell types — including alveolar macrophages, endothelial cells, and pericytes — that do not normally produce ACE2 or TMPRSS2, effectively equipping these recipient cells with the molecular tools required for viral entry. This discovery reveals a previously unknown mechanism by which SARS-CoV-2 can broaden its cellular targets in the lung, helping to explain the widespread tissue damage observed in severe COVID-19. The findings suggest that blocking EV-mediated transfer of these viral entry proteins could represent a novel therapeutic strategy to limit viral spread, and may have broader relevance for other viral infections that rely on similar entry mechanisms.
Nature communications
Source →Outcomes of patients with or without DNA repair pathway alterations: the MD Anderson IMPACT2 study.
Venturini J, et al
Researchers at MD Anderson Cancer Center analyzed data from the IMPACT2 study to determine how DNA damage response (DDR) gene alterations influence cancer patient outcomes depending on the type of treatment received. Among 662 patients with at least one genomic alteration, about 16.5% had DDR alterations while the remaining 83.5% were DDR wild-type. In patients with DDR alterations, immunotherapy (IO) was associated with significantly longer overall survival compared to chemotherapy or anti-DDR agents, and the absence of liver metastases also predicted better outcomes. In the DDR wild-type group, IO therapy likewise outperformed all other treatment categories, while normal albumin and lactate dehydrogenase levels and lack of liver metastases were additional favorable prognostic factors. These findings suggest that DDR alterations may serve as biomarkers to guide immunotherapy decisions, though the authors emphasize that prospective clinical trials are needed to confirm this role and refine patient selection strategies.
NPJ precision oncology
Source →Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.
Long G, et al
Researchers investigated how the liver is prepared to receive cancer metastases before tumor cells actually arrive, focusing on a protein called leucine-rich alpha-2-glycoprotein 1 (LRG1) produced by liver cells called hepatocytes. The study found that LRG1 is elevated in the blood of patients at higher risk of liver metastasis, and that this protein remodels the liver's microenvironment by accumulating immunosuppressive neutrophils, impairing cancer-fighting T cells and dendritic cells, and promoting new blood vessel growth. Mechanistically, tumor-driven inflammation activates IL-6/STAT3 signaling in hepatocytes to induce LRG1, which then triggers neutrophil extracellular traps through a TGFBR/PI3K/AKT signaling axis, collectively creating a hospitable environment for metastatic cancer cells. When LRG1 was genetically removed from hepatocytes in mouse models, premetastatic niche formation was disrupted and metastatic tumor burden was significantly reduced. Critically, therapeutic blocking of LRG1 not only suppressed liver metastasis but also converted the liver's immune environment from suppressive to activated, making tumors more responsive to anti-PD-1 checkpoint immunotherapy. These findings position LRG1 as a promising clinical target for both preventing and treating liver metastasis, as well as for improving the efficacy of existing immunotherapies.
Cellular & molecular immunology
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