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Tumour microenvironment

Immune suppression, metabolic competition, stroma and myeloid cells: how the tumour microenvironment decides response.

81 selectedRelated topicsImmunotherapySingle-cell and spatial omicsOncology

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41–60 of 81
Oct 3Sat
  1. medicalxpress.com60

    Inflammation can reactivate 'sleeping' cancer cells hidden in the bone

    Inflammation in the gut can wake dormant metastatic breast cancer cells in bone, according to work in Cell Reports using a new extramedullary bone model grown from skeletal stem cells in mice. Distant colitis drove immune cell production in the bone, and the growth-stimulating molecule HMGB2 rose and promoted reactivation of the sleeping cells; HMGB2 alone sufficed, and appeared alongside dividing cancer cells in human bone samples from people with breast or prostate cancer. The finding points to monitoring infections, inflammation or injury after remission as a marker of relapse risk.

    Why it matters: It identifies a molecular link between systemic inflammation and metastatic relapse that could guide post-remission monitoring.

Oct 2Fri
  1. Cancer Discovery67

    Senescent-Like Neutrophils Shape Angiogenic Immunosuppressive Niches in Colorectal Cancer Liver Metastasis

    A terminally differentiated protumor neutrophil subset, TAN1, marked by a glycolysis signature and senescent phenotype, is enriched in colorectal cancer liver metastasis and linked to poor prognosis. Single-cell and spatial-enhanced-resolution-omics sequencing show TAN1 arises from other tumor-associated neutrophil subsets via BHLHE40 upregulation driven by glucose deprivation, and promotes angiogenesis through VEGFA while recruiting immunosuppressive macrophages via CCL3L1-CCR1 signaling. Neutrophil-specific Bhlhe40 knockout in mice boosted antitumor immunity and suppressed tumor growth, pointing to a neutrophil-specific therapeutic target.

    Why it matters: It defines a targetable neutrophil subset and mechanism driving immunosuppression in colorectal cancer liver metastasis.

  2. Proc Natl Acad Sci U S A56

    PAK4 exacerbates melanoma immunosuppression by promoting exosome release

    PAK4 phosphorylates ANXA2 at Ser26, promoting its nuclear-to-cytoplasmic translocation and formation of S100A10-ANXA2 heterotetramers, while stabilizing synaptotagmin-1 by suppressing Trim21-mediated ubiquitin degradation. Through these actions it drives exosome release from multivesicular bodies and exacerbates melanoma immunosuppression.

    Why it matters: The paper defines a dual PAK4 mechanism of exosome-driven melanoma immunosuppression, supporting combination of PAK4 inhibitors with immune checkpoint blockade.

Oct 1Thu
  1. bioRxiv Cancer Biology64

    Early dynamics of a neutrophil interferon program drive immunotherapy resistance and limit durable anti-tumor immunity

    An interferon-stimulated gene program in neutrophils, detectable before tumors diverge in their response, predicts resistance to anti-PD1 therapy in preclinical triple-negative breast cancer models. Persistent neutrophil IFN signaling in blood and tumor tracked with treatment failure, while genetic disruption of type I or type II interferon signaling in neutrophils improved anti-PD1 efficacy and durable anti-tumor immune memory. The work positions IFN-responsive neutrophils as blood-based biomarkers and therapeutic targets.

    Why it matters: Identifies an early, blood-accessible neutrophil IFN signature that predicts anti-PD1 resistance and can be targeted.

  2. Cell64

    Spatial evolution of a cachexia-promoting microenvironment in pancreatic cancer.

    A defined multicellular niche in pancreatic tumors drives cachexia: SEMA4A+ tumor cells induce an AQP9+ macrophage phenotype via BMP2, macrophage-derived CXCL8 activates LOXL2+ fibroblasts, and those fibroblasts reinforce tumor FOSL1/SEMA4A signaling through exosomal N-glycosylated LOXL2. Integrating single-cell RNA sequencing, Xenium spatial transcriptomics, multiplex immunohistochemistry and functional studies in human samples and mouse models, the work shows the niche is progressively enriched with cachexia severity and predicts postoperative cachexia in previously non-cachectic patients. It supplies a spatially resolved circuit connecting the local tumor ecosystem to systemic wasting.

    Why it matters: It maps a spatially defined tumor niche that links pancreatic cancer progression to cachexia and its development.

  3. Oncoimmunology58

    A novel oncolytic peptide synergizing with immunotherapy

    Yuan et al. described in Nature an acid-responsive membranolytic peptide that separates lysosomal rupture from later plasma membrane rupture, turning oncolysis into immunogenic cell death. The design allows systemic administration, induces antigen-specific immunity and sensitizes tumors to programmed death ligand 1 blockade with limited toxicity.

    Why it matters: A preclinical Nature study shows an oncolytic peptide design that sensitizes tumors to PD-L1 blockade.

  4. Nature62

    Type 2 immune history trains lung macrophages for viral disease tolerance

    Type 2 inflammation trains nerve- and airway-associated macrophages to confer disease tolerance against lethal influenza. The trained macrophages limit immunopathology and promote tissue repair without enhancing viral clearance, indicating prior type 2 immune history protects through tolerance of infection rather than control of the virus itself.

    Why it matters: It separates disease tolerance from viral clearance as a mechanism for surviving influenza.

Sep 29Tue
  1. bioRxiv Genomics61

    Genomic correlates of metastatic competence and progression in human melanoma

    Metastatic competence in primary cutaneous melanoma is marked by somatic copy-number alterations and chromosomal instability rather than oncogenic point mutations, which were largely shared between primaries and metastases. Sequencing of 247 stage I/II primary melanomas and 60 matched metastases with median followup of 92 months yielded OncoCycle, a six-gene copy-number signature that predicted relapse independently of clinicopathological features. Matched pairs showed progression driven by continued copy-number evolution, with both monoclonal and polyclonal seeding resolved by clonal reconstruction.

    Why it matters: A six-gene copy-number signature predicts melanoma relapse and reframes metastasis as copy-number driven.

Sep 28Mon
  1. bioRxiv Cancer Biology67

    Disruption of the ARID1A-containing SWI/SNF complex reprograms tumor-associated macrophages and enhances immunotherapy response

    Disrupting the SWI/SNF chromatin remodeling complex in tumor-associated macrophages reprograms them and improves checkpoint blockade immunotherapy. Pharmacologic inhibition of SWI/SNF ATPase activity slowed tumor growth, and deleting the SWI/SNF subunit Arid1a in myeloid cells was sufficient to suppress tumor progression and enhance checkpoint blockade response. The reprogramming involved reduced enhancer accessibility at poor-prognosis genes such as Spp1, increased accessibility at interferon-stimulated gene promoters, elevated CD86, and required CD86 costimulation and CD8+ T cells.

    Why it matters: It identifies a druggable epigenetic target in macrophages that improves checkpoint blockade response.

  2. bioRxiv Cancer Biology58

    Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer

    Spatial transcriptomics of 49 primary DCIS specimens shows stromal cell gradients, with TREM2+ macrophages and myofibroblastic cancer-associated fibroblasts enriched in tumor-proximal niches. TREM2+ macrophage abundance near tumor nests is associated with recurrence as invasive breast cancer, and ligand-receptor analysis implicates GRN-SORT1, SPP1-CD44, and LGALS9-CD44 signaling between these macrophages and epithelial cells. Findings were validated by multiplex immunostaining.

    Why it matters: Identifies a spatially defined stromal biomarker for progression from DCIS to invasive breast cancer.

  3. bioRxiv Cancer Biology61

    Glutamine and GLS1 are key metabolic checkpoints that Limit T cell Infiltration and Function in HNSCC

    Glutaminase-1 acts as a metabolic checkpoint limiting T cell infiltration and function in head and neck squamous cell carcinoma (HNSCC). Pharmacologic inhibition or genetic deletion of glutaminase-1 increased tumor susceptibility to immune cell-mediated cytotoxicity and sensitized patient-derived tumor fragments to immune checkpoint blockade, via disruption of glutathione-dependent ROS defense, impaired tumor proliferation, and increased MHC expression. Breast cancer fragments, which show low glutaminase-1 expression, were not responsive, supporting patient stratification for metabolism-targeted immunotherapy.

    Why it matters: Identifies a targetable metabolic mechanism of immune checkpoint blockade resistance in HNSCC.

Sep 25Fri
  1. Cell Cycle31

    The role of fibronectin in the tumor microenvironment - implications for immunotherapy

    A review in Cell Cycle examines how oncofetal fibronectin isoforms containing the EDA and EDB domains shape the tumor microenvironment in solid tumors, where they are highly expressed but absent from normal adult tissues. It covers their roles in vascular remodeling, epithelial-mesenchymal transition, pre-metastatic niches and immunosuppression, and evaluates fibronectin as a biomarker and therapeutic target in breast cancer, ovarian cancer and glioblastoma. Stromal strategies including antibody-drug conjugates and immunocytokines are discussed as ways to overcome resistance to standard immunotherapy.

    Why it matters: Review links fibronectin in the tumor microenvironment to immunotherapy resistance and emerging ADC and immunocytokine targets.

  2. Nature Cancer53

    Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca 2+ activity

    Ischemic stroke generates a population of astrocytes with reduced calcium signaling, Lee and colleagues report. These astrocytes recruit tumor-associated macrophages, and this promotes glioma invasion in preclinical models. The work links stroke to glioma progression through a defined astrocyte-macrophage pathway.

    Why it matters: Identifies a mechanism by which stroke accelerates glioma invasion via altered astrocyte calcium signaling.

Sep 24Thu
  1. mp.weixin.qq.com65

    Tissue-resident macrophages feed pancreatic cancer cells Selenop to sustain invasiveness

    Tissue-resident macrophages enriched at the tumor boundary deliver the selenoprotein Selenop to highly invasive pancreatic ductal adenocarcinoma cells, helping them evade ferroptosis and maintain their invasive state. The finding reframes immune cells in the tumor microenvironment as nutrient and metabolic donors that directly sustain malignant cell behavior, not only as sources of cytokines and immune signals.

    Why it matters: Identifies a macrophage-to-tumor selenium supply axis that maintains PDAC invasiveness and ferroptosis resistance.

  3. Cell54

    Resident tissue macrophages transfer selenium transporter protein to protect pancreatic cancer from ferroptosis

    Resident tissue macrophages establish a selenium-rich microenvironment at the pancreatic tumor border and protect invasive tumor cells from ferroptosis by transferring the selenium transporter Selenop to epithelial-mesenchymal-transition-high (EMThi) cancer cells.

    Why it matters: New mechanism showing macrophage-transferred Selenop shields pancreatic cancer cells from ferroptosis.

Sep 23Wed
  1. medRxiv Oncology55

    Type 2 Deiodinase in Cancer-Associated Fibroblasts: A Potential Therapeutic Target in Many Types of Cancer

    Type 2 deiodinase (DIO2), the enzyme converting T4 to T3, is a conserved marker of cancer-associated fibroblasts (CAF) across thyroid cancer and six additional solid tumor types, and is enriched in myofibroblastic CAF. Elevated DIO2 expression correlated with worse overall survival in pancreatic and bladder cancers, while thyroid cancer showed an inverse association linked to loss of epithelial DIO2 during dedifferentiation. In a TPO-CreERT2/BrafV600E/Trp53-deficient mouse model, Dio2 loss in the tumor microenvironment significantly reduced tumor growth, and D2 activity was suppressed by cefuroxime and lenvatinib.

    Why it matters: Identifies DIO2 as a CAF-restricted, druggable target conserved across solid tumors, with preclinical evidence of tumor suppression.

Sep 22Tue
  1. Nature Cancer52

    Adipocyte methionine reduction promotes cancer cachexia

    Iron-activated MSRA is identified as a regulator of PKA in cancer cachexia. MSRA reduces oxidized PKA in white adipose tissue, thereby increasing PKA activity and promoting the wasting syndrome. The finding defines an upstream mechanism controlling PKA activation in adipocytes during cachexia.

    Why it matters: It identifies a mechanism controlling PKA activation in white adipose tissue during cancer cachexia.

Sep 21Mon
  1. medRxiv Oncology54

    Decidual-Like Natural Killer Cells Are Enriched in Melanomas and Acquire CD9 Through Melanoma Cell Contact

    Melanomas harbor decidual-like NK cells with a CD56 Bright CD16 - CD49a + CD9 + phenotype, a population rare or absent in peripheral blood from patients with melanoma and healthy donors. The cells appear in tumors across sex, melanoma subtype, and disease site, and tumor CD9 expression correlated with intratumoral dl-NK frequency (Pearson rho = 0.40, p = 0.056). Co-culture showed direct contact with CD9-expressing melanoma cells induces CD9 acquisition by NK cells, suggesting an immunologic parallel between melanoma and the maternal-fetal interface.

    Why it matters: It identifies a decidual-like NK cell population in melanoma and a contact-dependent mechanism for its induction.

Sep 18Fri
  1. Sci Adv69

    Targeting LOXL4-driven matrix stiffening with acetyldigoxin restores CD8+ T cell function in lung cancer.

    Tumor-derived LOXL4 stiffens the extracellular matrix in lung cancer, activating Piezo1 in CD8+ T cells and triggering Ca2+ influx with FAK1-YAP1 signaling that drives terminal exhaustion via YBX1, ACLY and KAT2A. Conditional knockout of Piezo1, Ybx1, Acly or Kat2a in murine CD8+ T cells abolished stiffness-induced exhaustion and suppressed tumor growth. Acetyldigoxin, identified by molecular docking as a high-affinity LOXL4 inhibitor among FDA-approved agents, softened the ECM, reversed CD8+ T cell exhaustion and synergized with anti-PD-1 blockade for durable tumor regression.

    Why it matters: It defines a mechanotransduction-to-epigenetic pathway of CD8+ T cell exhaustion and repurposes an FDA-approved drug against it.

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