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Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of

Robert Godal1, Ulrich Keilholz, Lutz Uharek

  • 1Department of Internal Medicine, St Elizabeth Oncological Institute, Bratislava, Slovakia.

Blood
|December 24, 2005
PubMed

Insights

Lymphoma cells expressing proteinase inhibitor 9 (PI-9) or bcl-2 remain sensitive to T-cell and NK-cell mediated killing. Resistance to these immune responses is not a significant factor in lymphoma immune escape.

Area of Science:

  • Immunology
  • Oncology
  • Cellular Biology

Background:

  • Lymphoma immune evasion strategies include proteinase inhibitor 9 (PI-9) and bcl-2 expression.
  • PI-9 inactivates granzyme B, while bcl-2 inhibits perforin-dependent cytotoxicity.

Purpose of the Study:

  • To analyze the impact of PI-9 and bcl-2 expression on lymphoma sensitivity to T-cell and natural killer (NK) cell cytotoxicity.
  • To determine if these molecules represent relevant immune escape mechanisms in lymphoma.

Main Methods:

  • Analysis of PI-9 and bcl-2 expression in lymphoma cell lines and primary lymphomas.
  • Assessment of lymphoma cell sensitivity to cytolysis by specific T cells and activated/resting NK cells.
  • Investigation of the cytotoxic pathways involved, including perforin-dependent mechanisms.

Main Results:

  • PI-9 was expressed in 10/18 cell lines and 9/14 primary lymphomas; bcl-2 was overexpressed in 8/18 cell lines and 12/14 primary lymphomas.
  • All lymphoma cells were sensitive to T-cell and cytokine-activated NK cell-mediated lysis, irrespective of PI-9 or bcl-2 levels.
  • Cytolysis primarily occurred via perforin-dependent pathways, even with PI-9 and bcl-2 present.
  • Lymphoma cells showed resistance to resting allogeneic NK cells due to failed NK cell degranulation.

Conclusions:

  • Lymphoma resistance to perforin-dependent pathways is not a significant immune escape mechanism.
  • PI-9 and bcl-2 expression do not impair lymphoma sensitivity to T-cell and activated NK cell cytotoxicity.
  • These findings suggest that PI-9 and bcl-2 are unlikely to negatively impact immunotherapeutic approaches for lymphoma.

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