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Lymphocyte-Melanoma Interaction: Role of Surface Molecules

  • J. C. Becker
  • E. B. Bröcker
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 139)

Abstract

The coexistence of tumor-speciic immunity with a progressing tumor is observed in most experimental systems and remains one of the major paradoxes of tumor immunology. Expression of several surface molecules on melanoma cells, e.g., intercellular adhesion molecule 1 (ICAM-1) or major histocompatibility complex (MHC) class II, has been associated with an aggressive tumor growth and an reduced host antitumor response.

HLA class I expression is also frequently altered in melanoma compared to melanocytes. Given the central role of these molecules in the restriction of T cell recognition, regulation of tumor HLA class I expression might also be a strategy for the evasion of immune surveillance by the malignant cells.

The fact that it is now possible to clone antigen-specific T cells from tumor patients, as well as the relevant autologous tumor cell lines, enabled us to establish a model system to investigate possible tumor escape mechanisms from immunosurveillance.

Using this system, we were able to demonstrate that purified soluble ICAM-1 or 12-fold-concentrated cell-free melanoma supernatants, containing shed ICAM-1, were able to inhibit conjugate formation between T cell clones and the autologous melanoma cells as efficiently as monoclonal antibodies against CD11a, Soluble ICAM-1 also abrogated the MHC-restricted killing of the melanoma by T cell clones.

We further observed that a number of CD4+ T cell clones and melanoma cell lines established from the same tumors form conjugates with each other, leading to an increase of [Ca2+]i in the T cell clone; however, this interaction failed to induce interleukin-2 production or proliferation of the T cell clone. Furthermore, this interaction rendered the T cell clone unresponsive to subsequent stimulation. All these effects were MHC class II restricted. Therefore, the melanoma was capable of delivering antigen-specific signals to the T cell clone, but did not deliver the costimulatory signals, e.g., a dere hingegen führen den Unterschied auf die pragmatische Haltung der Richter zurück, die im State Farm Fall den „bad smell” der zu überprüfenden Entscheidung wahrgenommen hätten, während sie im. Baltimore Gas Fall die intensive und redliche Erörterung der aufgeworfenen Frage honoriert hätten183.

Keywords

Major Histocompatibility Complex Melanoma Cell Major Histocompatibility Complex Class Cell Clone Melanoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin · Heidelberg 1995

Authors and Affiliations

  • J. C. Becker
    • 1
  • E. B. Bröcker
    • 1
  1. 1.Department of DermatologyUniversity of WürzburgWürzburgGermany

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