ArticleBMC cancer2021
Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 13 citations in OpenAlex.
- Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial.Blood advances · 2023Trial
- Advances in biomarkers for mantle cell lymphoma in the era of targeted therapies.Haematologica · 2026Review
- Regulatory T Cell-Related Gene Polymorphisms are Associated with Risk of Lung Cancer in Patients with COPD.International journal of chronic obstructive pulmonary disease · 2026Article
- Single-cell RNA Sequencing Analysis Reveals the Molecular Mechanisms of Neutrophil Dysfunction in Chronic Bone Infection.Current medicinal chemistry · 2026Article
- Innovative approach for the qualitative-quantitative assessment of neurodevelopment biomarkers research in placenta tissue using immunohistochemistry digital image analysis.Biology methods & protocols · 2025Article
- Development of a novel prognostic model for mantle cell lymphoma based on quantitative detection of CD3 by quantitative dot blot.Frontiers in oncology · 2025Article
- Lymph node metastasis in patients with hepatocellular carcinoma using machine learning: a population-based study.Frontiers in oncology · 2025Article
- Article
- Review
- Ferroptosis-related prognostic model of mantle cell lymphoma.Open medicine (Warsaw, Poland) · 2024Article
- Immune-depleted tumor microenvironment is associated with poor outcomes and BTK inhibitor resistance in mantle cell lymphoma.Blood cancer journal · 2023Article
- Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma.Annals of translational medicine · 2022Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThere is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients' samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL.
methodsWe assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models.
resultsHigh FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFβ levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients' survival.
conclusionsOur results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.
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