bims-gerecp 2026-10-25 papers

Issue of 2026–10–25
seven papers selected by
Xiao Qin, University of Oxford

Cancer Cell. 2026 Oct 22. pii: S1535-6108(26)00398-3. [Epub ahead of print]

How far are we from multi-omics states to therapeutic targets in microsatellite-stable colorectal cancer?

In this issue of Cancer Cell, Sadanandam et al. integrate multi-omics profiling of microsatellite-stable colorectal cancer with patient-derived models, identifying focal adhesion kinase and phosphoinositide-dependent kinase 1 as promising therapeutic targets. The study advances multi-omics discoveries toward functional precision oncology and potential treatment strategies to guide clinical translation.

DOI: https://doi.org/10.1016/j.ccell.2026.09.001

STAR Protoc. 2026 Oct 20. pii: S2666-1667(26)00517-4. [Epub ahead of print]7(4): 104864

An improved protocol to isolate enriched immune cells from murine intestinal epithelium and lamina propria.

Sydney B Crotts, Virginia Smith Shapiro.

The intestine is home to more immune cells than any other non-lymphatic peripheral tissue, but research of these cells is stymied by the technical difficulties involved in isolating them. Here, we describe a protocol to isolate highly viable immune cells from murine intestinal epithelium and lamina propria. This protocol can be used to characterize cells by flow cytometry or single-cell transcriptomics, as in Crotts et al., or by other analysis methods.

Keywords: Cell isolation; Cell separation/fractionation; Flow Cytometry; Immunology

DOI: https://doi.org/10.1016/j.xpro.2026.104864

Cell Syst. 2026 Oct 20. pii: S2405-4712(26)00239-5. [Epub ahead of print] 101757

Asymmetric crosstalk between the BMP and TGF-β pathways resolves signaling ambiguity.

Johannes M Auth, Inbal Eizenberg-Magar, Omer Erez Dekel, Omer Zachar, Merav D Shmueli, Inbal Zigdon, Achinoam Shoham, Vladimir Mindel, Tsviya Olender, Meytar Asulin Berrebi, Ariel Tennenhouse, Neta Bar-Hai, Rakefet Ben-Yishay, Dana Ishay-Ronen, Yaron E Antebi.

The BMP and TGF-β signaling pathways control cellular fate decisions in diverse biological contexts, often playing opposing roles. Despite extensive knowledge of these pathways, understanding how cells respond to environments containing these opposing cues remains a challenge. Here, we systematically analyze the activation of these pathways under combinatorial signaling environments. We find that TGF-β ligands inhibit BMP signaling while BMP ligands enhance TGF-β transcriptional response across concentrations, ligand variants, and cell types. This asymmetric crosstalk results in the activation of a TGF-β-biased transcriptional response even under mixed-signaling conditions, effectively reducing signal ambiguity, with implications for processes such as epithelial-to-mesenchymal transition (EMT). We show that this crosstalk originates downstream of SMAD protein phosphorylation. Using mathematical models, we predict and experimentally verify that promiscuous interactions between SMAD proteins provide the mechanism for the observed crosstalk. Our findings challenge the canonical models, suggesting an active role for mediator proteins in determining biological responses.

Keywords: BMP signaling; SMAD complexes; TGF-β; combinatorial signaling; mathematical modeling; signal integration; signaling; signaling crosstalk

DOI: https://doi.org/10.1016/j.cels.2026.101757

Trends Cancer. 2026 Oct 20. pii: S2405-8033(26)00218-9. [Epub ahead of print]

The tumor macroenvironment as cancer metabolism's next frontier.

Allison B Grenell, Joe L Rowles, Ronnie Fowle-Grider, Yin Cao, Leah P Shriver, Gary J Patti.

The deregulated utilization of nutrients by tumors, first observed over a century ago, is recognized as a hallmark of cancer and continues to be exploited clinically to image neoplastic disease. Despite this historic focus on cancer cells and, more recently, their neighbors, metabolic reprogramming is not limited to the tumor microenvironment. Tumors also have the capacity to rewire the metabolism of cells throughout the body, including those at distant sites, often referred to as the tumor macroenvironment. Alterations in the metabolism of noncancerous tissues outside the local tumor ecosystem are gaining attention, but their origins and consequences remain incompletely defined. A deeper understanding of these changes may reveal previously unrecognized signatures of disease and unexplored opportunities for therapeutic intervention.

Keywords: cachexia; glucose; glutamine; lipids; tumor macroenvironment; whole-body metabolism

DOI: https://doi.org/10.1016/j.trecan.2026.09.007

Trends Cancer. 2026 Oct 19. pii: S2405-8033(26)00220-7. [Epub ahead of print]

MAIT cells in gastrointestinal cancer: immunity to therapy.

Yan-Ruide Li, Yuning Chen, Shelby Yeh, Thomas Yuen, Lili Yang.

Mucosal-associated invariant T (MAIT) cells are emerging as important regulators of immunity in gastrointestinal (GI) cancers. Enriched in mucosal and hepatic tissues, MAIT cells recognize microbial-derived metabolites presented by MHC class I-related molecule (MR1) and rapidly exert effector functions, including cytokine production and cytotoxicity. Across GI malignancies, including hepatocellular carcinoma, cholangiocarcinoma, colorectal, gastric, pancreatic, and esophageal cancers, MAIT cells display context-dependent roles shaped by the tumor microenvironment, microbiome, and immune signaling pathways. While they can mediate antitumor immunity, they frequently exhibit functional exhaustion or adopt pro-tumorigenic phenotypes. Therapeutic strategies aim to enhance MAIT cell activity, reverse dysfunction, and integrate them into combinatorial immunotherapy approaches. Understanding MAIT cell biology may enable their exploitation as biomarkers and therapeutic targets in GI cancers.

Keywords: GI cancer; MAIT cells; MR1; TME; microbial metabolites; mucosal immunology

DOI: https://doi.org/10.1016/j.trecan.2026.09.009

Nat Commun. 2026 10 20. pii: 10956. [Epub ahead of print]17(1):

Epithelial NF-κB shapes protective Treg cell responses to restrain intestinal inflammation.

Inflammation resolution depends on coordinated communication between tissue compartments, yet how the intestinal epithelium shapes its immune microenvironment remains poorly understood. Here, using colonic biopsies from patients with ulcerative colitis (UC) and mouse models enabling tissue-wide visualization of NF-κB activity, we combine single-cell RNA sequencing and secretome analysis to define epithelial communication during colitis. We show that, paradoxically, the NF-κB-driven pro-inflammatory secretome of intestinal epithelial cells (IECs) is essential for recovery and prevents unrestrained inflammation. Mechanistically, epithelial NF-κB promotes CCL22-dependent regulatory T cell (Treg cell) recruitment and promotes a tolerogenic, pro-repair cell state, accompanied by induction of the lipid-metabolism-associated GDPD3 and CCR4. In UC, epithelial NF-κB is not uniformly activated but instead induces a selective pro-inflammatory transcriptional program while repressing targets regulating T cell recruitment. Thus, we identify dynamic epithelial-immune communication and demonstrate a protective IEC NF-κB-Treg cell axis important for resolution of intestinal inflammation.

DOI: https://doi.org/10.1038/s41467-026-78796-z