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WNT7A correlates with immunosuppression and predicts adverse prognosis in lung adenocarcinoma: Potential implication of the NF-kappaB/CCL2 Axis
Cytokine. 2026 Apr 6;202:157144. doi: 10.1016/j.cyto.2026.157144. Online ahead of print.
ABSTRACT
BACKGROUND: The remodeling of the tumor immune microenvironment (TME) is a pivotal determinant of therapeutic efficacy and clinical outcome in Lung Adenocarcinoma (LUAD). While WNT signaling is a known oncogenic driver, the specific immunomodulatory role of WNT7A and its potential crosstalk with inflammatory pathways in LUAD remain to be fully elucidated. We sought to define the prognostic value of WNT7A and explore the molecular mechanisms by which it may foster an immunosuppressive TME.
METHODS: We performed a multi-omics analysis utilizing the TCGA-LUAD cohort (N = 508) and validated findings in an independent external cohort (GSE30219, N = 293). The prognostic significance of WNT7A was evaluated using Kaplan-Meier and multivariate Cox regression analyses. TME composition was dissected via ssGSEA, focusing on myeloid-derived suppressor cell (MDSC) infiltration. Mechanistic pathways were identified using Gene Set Enrichment Analysis (GSEA) and gene co-expression networks.
RESULTS: High WNT7A expression was identified as a significant predictor of poor Overall Survival (OS) in the TCGA cohort (P < 0.05) and validated in the external cohort (P < 0.05). Multivariate analysis confirmed WNT7A as an independent prognostic risk factor (HR = 1.085, P = 0.036). Immunologically, WNT7A expression was positively correlated with MDSC infiltration (R = 0.43, P < 0.001), suggesting a shift towards an immune-tolerant phenotype. Mechanistically, GSEA revealed a robust activation of inflammatory signaling in the high-WNT7A group. Specifically, the TNFA Signaling via NF-κB pathway was significantly enriched(NES = 2.52, P < 0.001). Consistent with this pathway activation, WNT7A showed a statistically significant positive correlation with CCL2 (P < 0.001), a critical chemokine for MDSC recruitment, implicating the NF-κB/CCL2 axis in this process.
CONCLUSION: WNT7A serves as a prognostic biomarker linked to immune evasion in LUAD, potentially by modulating the NF-κB/CCL2/MDSC axis. This study identifies WNT7A as a potential therapeutic target to remodel the immune microenvironment, providing a rationale for future investigations into WNT-targeted strategies to improve immunotherapy efficacy.
PMID:41946008 | DOI:10.1016/j.cyto.2026.157144
Iron Physiology and Its Impact on Atopic Diseases: An EAACI Taskforce Report
Allergy. 2026 Apr 6. doi: 10.1111/all.70325. Online ahead of print.
ABSTRACT
Iron is essential for oxygen transport, energy metabolism, and immune regulation. Yet iron deficiency is the most common micronutrient disorder across all age groups, affecting nearly one quarter of the global population. Iron deficiency triggers nutritional immunity, a host defense mechanism that withholds and redistributes iron, contributing to increased morbidity and mortality. This review outlines normal iron physiology, distribution and absorption pathways and on the consequences of deficiency across body compartments, with particular attention to type 2-driven diseases. Beyond anemia, insufficient iron availability disrupts immune homeostasis by promoting type 2 inflammation, elevating IgE, and activating mast cells and eosinophils. Regulatory macrophages, the central hub of iron cycling, adopt an inflammatory, iron-sequestering state that reinforces malabsorption and redistribution. Epidemiology studies show higher iron-deficiency risk in allergic individuals; low maternal iron or early-life iron predisposes to eczema, wheeze, and asthma, while food-allergen elimination (notably cow's milk) further worsens anemia risk. Clinical evidence indicates that restoring iron status through diet, supplementation, or fortification lowers IgE levels, improves lung function, and alleviates symptoms of rhinitis, urticaria, and asthma. Iron may therefore represent a modifiable determinant of allergic disease development and severity. Integrating iron assessment and nutritional care into allergy management may reduce disease burden and slow the progression of allergic march.
PMID:41943501 | DOI:10.1111/all.70325
WNT7A correlates with immunosuppression and predicts adverse prognosis in lung adenocarcinoma: Potential implication of the NF-kappaB/CCL2 Axis
Cytokine. 2026 Apr 6;202:157144. doi: 10.1016/j.cyto.2026.157144. Online ahead of print.
ABSTRACT
BACKGROUND: The remodeling of the tumor immune microenvironment (TME) is a pivotal determinant of therapeutic efficacy and clinical outcome in Lung Adenocarcinoma (LUAD). While WNT signaling is a known oncogenic driver, the specific immunomodulatory role of WNT7A and its potential crosstalk with inflammatory pathways in LUAD remain to be fully elucidated. We sought to define the prognostic value of WNT7A and explore the molecular mechanisms by which it may foster an immunosuppressive TME.
METHODS: We performed a multi-omics analysis utilizing the TCGA-LUAD cohort (N = 508) and validated findings in an independent external cohort (GSE30219, N = 293). The prognostic significance of WNT7A was evaluated using Kaplan-Meier and multivariate Cox regression analyses. TME composition was dissected via ssGSEA, focusing on myeloid-derived suppressor cell (MDSC) infiltration. Mechanistic pathways were identified using Gene Set Enrichment Analysis (GSEA) and gene co-expression networks.
RESULTS: High WNT7A expression was identified as a significant predictor of poor Overall Survival (OS) in the TCGA cohort (P < 0.05) and validated in the external cohort (P < 0.05). Multivariate analysis confirmed WNT7A as an independent prognostic risk factor (HR = 1.085, P = 0.036). Immunologically, WNT7A expression was positively correlated with MDSC infiltration (R = 0.43, P < 0.001), suggesting a shift towards an immune-tolerant phenotype. Mechanistically, GSEA revealed a robust activation of inflammatory signaling in the high-WNT7A group. Specifically, the TNFA Signaling via NF-κB pathway was significantly enriched(NES = 2.52, P < 0.001). Consistent with this pathway activation, WNT7A showed a statistically significant positive correlation with CCL2 (P < 0.001), a critical chemokine for MDSC recruitment, implicating the NF-κB/CCL2 axis in this process.
CONCLUSION: WNT7A serves as a prognostic biomarker linked to immune evasion in LUAD, potentially by modulating the NF-κB/CCL2/MDSC axis. This study identifies WNT7A as a potential therapeutic target to remodel the immune microenvironment, providing a rationale for future investigations into WNT-targeted strategies to improve immunotherapy efficacy.
PMID:41946008 | DOI:10.1016/j.cyto.2026.157144
STAT+: FDA backs proposals to entice pharma companies to test, make drugs domestically
WASHINGTON — The Food and Drug Administration used the president’s budget to propose policies aimed at encouraging domestic development and manufacturing of drugs.
FDA Commissioner Marty Makary has said the agency needs “giant, big ideas” to counter China’s dominance in early-stage clinical development of drugs. Among the FDA’s ideas are proposals to make it easier to run early-stage trials in the U.S. and to hand an advantage to U.S.-based generics manufacturers.
The Trump administration has been using a variety of policy levers to try and bring drug manufacturing to the U.S. For example, many of the brand drugmakers that struck deals to lower U.S. prices also promised to increase domestic manufacturing, under the threat of tariffs.
Continue to STAT+ to read the full story…


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