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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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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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T cell immunity induced by live, necrotic, and apoptotic tumor cells

Wolf C Bartholomae1, Frauke H Rininsland, Julia C Eisenberg

  • 1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|July 9, 2004
PubMed

Insights

Tumor cell death, whether apoptotic or necrotic, does not alter antitumor immunity. The tumor

Area of Science:

  • Immunology
  • Cancer Research
  • Cell Biology

Background:

  • Antitumor immunity engagement rules are not fully understood.
  • Tumor antigens can induce T cell tolerance without innate immune activation.
  • The role of innate immune system engagement in antitumor responses is unclear.

Purpose of the Study:

  • Investigate how tumor cell death affects immunogenicity.
  • Determine the impact of live, apoptotic, and necrotic tumor cells on T cell responses.
  • Clarify whether tumor cell death signals influence antitumor immunity.

Main Methods:

  • Utilized murine melanoma (B16m) and lymphoma (L5178Y-R) models.
  • Injected live, apoptotic, and necrotic tumor cells into syngeneic mice.
  • Analyzed clonal sizes and cytokine signatures of induced T cells.

Main Results:

  • Live tumors induced a type 2 CD4 T cell response (IL-2, IL-4, IL-5 dominant over IFN-gamma).
  • Live, apoptotic, and necrotic cells induced comparable CD4 T cell frequencies and profiles, without CD8 T cell induction.
  • A specific tumor subclone (L5178Y-S) induced a protective type 1 response involving both CD4 and CD8 T cells.

Conclusions:

  • Tumor cell death (apoptotic or necrotic) does not primarily govern antitumor immune response magnitude or quality.
  • Tumor immunogenicity and type 1/type 2, CD4/CD8 cell immunity induction are intrinsic tumor features.
  • Innate immune system engagement by tumor cell death does not significantly alter antitumor immunity outcomes.

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