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Self antigens expressed by solid tumors Do not efficiently stimulate naive or activated T cells: implications for
D E Speiser1, R Miranda, A Zakarian
1Ontario Cancer Institute, Department of Medical Biophysics and Department of Immunology, University of Toronto, Ontario M5G 2M9, Canada.
The Journal of Experimental Medicine
|August 29, 1997
Summary
This study shows that tumors can evade cytotoxic T lymphocyte (CTL) responses, necessitating repeated immunotherapy for effective antitumor activity. The findings suggest limited risk for autoimmune diseases, encouraging targeted cancer treatments.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Pancreatic beta-cell tumors were induced using simian virus 40 T antigen (Tag) under the rat insulin promoter (RIP).
- Lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) was introduced as an endogenous tumor antigen.
Purpose of the Study:
- To investigate the induction and maintenance of cytotoxic T lymphocyte (CTL) activity against an endogenous tumor in vivo.
- To assess the efficacy of LCMV infection in generating an antitumor CTL response.
- To evaluate the sustainability of the CTL response and the potential for immunotherapy.
Main Methods:
- Generation of double transgenic RIP(GP x Tag2) mice expressing both Tag and LCMV-GP.
- Induction of LCMV infection to stimulate an antitumor CTL response.
- Monitoring tumor mass, blood glucose levels, survival, and CTL activity.
- Adoptive transfer of activated spleen cells.
Main Results:
- LCMV infection induced a transient antitumor CTL response, reducing tumor mass and prolonging survival in RIP(GP x Tag2) mice.
- The CTL response was not sustained despite continued tumor antigen and MHC class I expression.
- Adoptive transfer of activated cells further improved survival, confirming antigen presence and CTL capability.
- Tumors demonstrated a profound lack of spontaneous CTL induction and maintenance, indicating poor immunogenicity.
Conclusions:
- Endogenous tumors may evade immune surveillance by failing to induce or maintain CTL responses.
- Repetitive immunizations are crucial for sustained antitumor immunotherapy.
- The limited risk of autoimmune disease suggests potential for immunotherapy targeting tumor-associated antigens.