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Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
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Tumor-released survivin induces a type-2 t cell response and decreases cytotoxic T cell function, in vitro

Jessica M S Jutzy1, Salma Khan, Malyn May Asuncion-Valenzuela

  • 1Center for Health Disparities & Molecular Medicine, Department of Basic Sciences, Loma Linda University, 11085 Campus Street, Mortensen Hall Room 162, Loma Linda, CA, 92350, USA.

Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society
|February 11, 2012
PubMed

Insights

Tumor-released Survivin, an inhibitor of apoptosis protein, alters T cell responses. This protein shifts T cell profiles from type 1 to type 2, decreasing cytotoxic T cell function in cancer patients.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Clinical studies reveal a shift towards type-2 T cell responses and reduced cytotoxic T cell function in cancer patients.
  • The underlying cause of this immunosuppressive T cell skewing in cancer remains largely unknown.

Purpose of the Study:

  • To investigate the role of tumor-released Survivin in modulating T cell responses.
  • To determine if Survivin directly impacts T cell proliferation, function, and cytokine production.

Main Methods:

  • In vitro T cell cultures were treated with Survivin, a tumor-specific antigen and inhibitor of apoptosis protein.
  • Analysis of T cell proliferation, cytotoxic CD8(+) T cell function, and cytokine profiles (IFN-γ, IL-2, IL-4).
  • Assessment of Th17 and T regulatory cell populations and function.

Main Results:

  • Survivin addition to T cell cultures decreased T cell proliferation and cytotoxic CD8(+) T cell function.
  • Significant reduction in type 1 T cell numbers and associated cytokines (IFN-γ, IL-2) was observed.
  • Increased IL-4 release and type 2 T cell numbers, indicating a shift in T cell polarity.

Conclusions:

  • Tumor-derived Survivin directly modulates T cells, promoting a type-2 immune response.
  • This Survivin-induced T cell phenotype mirrors the immune dysregulation observed in cancer patients.
  • Survivin represents a potential therapeutic target for restoring anti-tumor immunity.

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