MMP2 is a immunotherapy related biomarker and correlated with cancer-associated fibroblasts infiltrate in melanoma

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Feb. 14, 2023

Abstract Background Mounting evidence supports that matrix metalloproteinase (MMPs) are highly associated with tumor progression and targeting MMPs may overcome the barrier of immune suppression. Among these, whether MMP2 functions as an immunosuppressive role in melanoma, remains unclear. Methods The Cancer Genome Atlas (TCGA) Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to assess prognosis after which Tumor estimation resource (TIMER) was explore relationship between expression cancer fibroblasts (CAFs) infiltration. Finally, we evaluated efficacy inhibitor on CAFs infiltration immunotherapy using a mouse melanoma model. Results In general, MMP2, MMP13, MMP16, MMP17 MMP25 significantly skin cutaneous (SKCM) patients prognosis, among low benefited most. Especially, overall survival (OS) BRAF mutation high lower than group, but there no significant difference wild-type patients. KEGG GO enrichment analysis indicated related genes mostly extracellular structure organization, collagen-containing structural constituent. Furthermore, almost all cancers, positively correlated works synergistically PD-1 antibody induces regression model, is dependent decreased Conclusions This suggests plays vital regulation infiltration, potentially participating response, thus representing valuable target melanoma.

Language: Английский

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Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 1, 2024

Abstract Lipid metabolism in cancer cells has garnered increasing attention recent decades. Cancer thrive hypoxic conditions, nutrient deficiency, and oxidative stress cannot be separated from alterations lipid metabolism. Therefore, exhibit increased metabolism, uptake, lipogenesis storage to adapt a progressively challenging environment, which contribute their rapid growth. Lipids aid cell activation. absorb lipids with the help of transporter translocase proteins obtain energy. Abnormal levels series synthases over-accumulation tumor microenvironment (TME). reprogramming plays an essential role TME. are closely linked several immune phenotypic transformation. The further promotes immunosuppression, leads escape. This event significantly affects progression, treatment, recurrence, metastasis cancer. present review describes TME examines connection between immunotherapy.

Language: Английский

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Tumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer

EBioMedicine, Journal Year: 2024, Volume and Issue: 101, P. 105003 - 105003

Published: Feb. 9, 2024

Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients NSCLC and the efficacy of immune checkpoint blockade (ICB) cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing epithelial

Language: Английский

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Cancer-associated fibroblast spatial heterogeneity and EMILIN1 expression in the tumor microenvironment modulate TGF-β activity and CD8⁺ T-cell infiltration in breast cancer

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 1873 - 1885

Published: Jan. 1, 2024

Rationale:The tumor microenvironment (TME) and its multifaceted interactions with cancer cells are major targets for treatment.Single-cell technologies have brought insights into the TME, but resulting complexity often precludes conclusions on function.Methods: We combined single-cell RNA sequencing spatial transcriptomic data to explore relationship between different cancer-associated fibroblast (CAF) populations immune cell exclusion in breast tumors.The significance of findings was then evaluated a cohort tumors (N=75) from patients using immunohistochemistry analysis.Results: Our show first time degree organization CAF cancer.We found that IL-iCAFs, Detox-iCAFs, IFNγ-iCAFs tended cluster together, while Wound-myCAFs, TGFβ-myCAFs, ECM-myCAFs formed another group overlapped elevated TGF-β signaling.Differential gene expression analysis areas CD8 + T-cell infiltration/exclusion within signaling-rich zones identified elastin microfibrillar interface protein 1 (EMILIN1) as top modulated gene.EMILIN1, inhibitor, upregulated directly modulating TGFβ immunosuppressive function.Histological 75 samples confirmed high EMILIN1 margins related infiltration, consistent our analysis.High also associated better prognosis cancer, underscoring functional recruitment cytotoxic T area. Conclusion:Our correlating signaling subpopulation is not enough because proteins TGF-β-modulating activity originating other subpopulations can alter activity.Therefore, therapeutic targeting should remain focused biological processes rather than specific subtypes.

Language: Английский

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[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2024, Volume and Issue: 51(7), P. 1981 - 1988

Published: Feb. 20, 2024

Language: Английский

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