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Soluble Fibrin Inhibits Lymphocyte Adherence and Cytotoxicity Against Tumor Cells: Implications for Cancer Metastasis and Immunotherapy

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee, jbiggers{at}utk.edu

Brandy Weidow, MS

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee

Judith Dexheimer, BS

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee

Gary Warnes, PhD

Flow Cytometry and Imaging Core Facilities, Institute of Cell and Molecular Science, Queen Mary University of London, London, UK

Jacqueline Vidosh, BS

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee

Shonak Patel, MD

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee

Michael Newman, MS

University of Tennessee Statistics Consulting Center, University of Tennessee, Knoxville, Tennessee

Pretesh Patel, BS

Biological Imaging Unit, University of Tennessee, Knoxville, Tennessee

Circulating soluble fibrin (sFn) is elevated in many cancer patients. It is a marker for ongoing disseminated intravascular coagulation and may have prognostic significance. We have demonstrated that sFn inhibited monocyte adherence and cytotoxicity by a mechanism involving blockade of monocyte Mβ2 and tumor cell CD54. It was, therefore, hypothesized that sFn also inhibits lymphocyte and interleukin-2—activated lymphocyte (LAK) adherence and cytotoxicity against tumor cells. This study sought to identify the lymphocyte subset responsible for adherence and killing of A375 melanoma cells and whether sFn inhibited these parameters. Lymphocyte and LAK cell adherence and cytotoxicity, which was adherence dependent, were inhibited by preincubation with purified or plasma-derived sFn. The lymphocyte and LAK cell activities were primarily a result of CD8⁺ MHC (major histocompatibility complex) unrestricted cytotoxic T cells. These results suggest that elevated levels of circulating sFn may be immunosuppressive and may reduce the efficacy of adoptive immunotherapies.

Key Words: lymphocyte • cancer • metastasis • fibrin • immunosuppression

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