ArticleThe Journal of investigative dermatology2013
Vascular E-selectin expression correlates with CD8 lymphocyte infiltration and improved outcome in Merkel cell carcinoma.
Article in The Journal of investigative dermatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates.American journal of clinical dermatology · 2024Review
- Single-cell adhesive profiling in an optofluidic device elucidates CD8Cell reports methods · 2024Article
- Tumor-associated CD8Frontiers in immunology · 2024Article
- Adhesion analysis via a tumor vasculature-like microfluidic device identifies CD8Cell reports · 2023Article
- Modulation of T cell function and survival by the tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- Insights into anti-tumor immunityFrontiers in immunology · 2023Review
- Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response.Journal of clinical medicine · 2022Review
- Merkel cell polyomavirus and associated Merkel cell carcinoma.Tumour virus research · 2022Review
- Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.International journal of hematologic oncology · 2022Review
- Review
- T-Cell Responses in Merkel Cell Carcinoma: Implications for Improved Immune Checkpoint Blockade and Other Therapeutic Options.International journal of molecular sciences · 2021Review
- Quality Is King: Fundamental Insights into Tumor Antigenicity from Virus-Associated Merkel Cell Carcinoma.The Journal of investigative dermatology · 2021Review
- Merkel Cell Polyomavirus and Merkel Cell Carcinoma.Cancers · 2020Review
- Selective reactivation of STING signaling to target Merkel cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Migration and Function of Memory CD8The Journal of investigative dermatology · 2020Review
- Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms.Frontiers in oncology · 2020Review
- Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma.BMJ case reports · 2019Article
- Review
- Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment.Frontiers in immunology · 2019Review
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8 authors at 5 institutions in 2 countries.
Funding
Abstract
Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-linked skin cancer. Although CD8 lymphocyte infiltration into the tumor is strongly correlated with improved survival, these cells are absent or sparse in most MCCs. We investigated whether specific mechanisms of T-cell migration may be commonly disrupted in MCC tumors with poor CD8 lymphocyte infiltration. Intratumoral vascular E-selectin, critical for T-cell entry into skin, was downregulated in the majority (52%) of MCCs (n=56), and its loss was associated with poor intratumoral CD8 lymphocyte infiltration (P<0.05; n=45). Importantly, survival was improved in MCC patients whose tumors had higher vascular E-selectin expression (P<0.05). Local nitric oxide (NO) production is one mechanism of E-selectin downregulation and it can be tracked by quantifying nitrotyrosine, a stable biomarker of NO-induced reactive nitrogen species (RNS). Indeed, increasing levels of nitrotyrosine within MCC tumors were associated with low E-selectin expression (P<0.05; n=45) and decreased CD8 lymphocyte infiltration (P<0.05, n=45). These data suggest that one mechanism of immune evasion in MCC may be restriction of T-cell entry into the tumor. Existing therapeutic agents that modulate E-selectin expression and/or RNS generation may restore T-cell entry and could potentially synergize with other immune-stimulating therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.