Related Experiment Videos
Defects in cell-mediated immunity during growth of a syngeneic simian virus-induced tumor
Abstract:
Four assays of tumor-specific cell-mediated immunity were compared during growth of a syngeneic Simian-virus-40-induced tumor, mKSA. Major differences were found in immunity detected by the tumor neutralization test (the Winn test), direct tumor challenge, the microcytotoxicity assay and the -51chromium-release lymphocytotoxicity assay. Progressive growth of the neoplasm followed by loss of immunity (the eclipse phenomenon) was documented with the Winn test. It was established that this eclipse phenomenon represented a lesion in the T-cell system of tumor-bearing hosts. This lesion was found to be specific and unrelated to anatomic tumor location. The ability to produce graft-versus-host reactions, and the ability to respond to mitogens, were found to be generally intact in tumor-bearing animals. Cells capable of recognizing mKSA tumor antigens and reconstituting an immune response following surgical removal of tumor or upon transfer to normal mice were found in the spleens of mice bearing advanced tumors. No suppressor cells that might account for the eclipse phenomenon could be demonstrated. Tumor-bearer serum did not block neutralizing activity of immune spleen cells in the Winn test, and immune cells were capable of neutralizing tumor even in tumor-bearing hosts. The possibility that the lesion is intrinsic to T-cell precursors of effector cells is discussed.
Insights
Tumor growth impairs T-cell immunity, causing an "eclipse phenomenon" where immune responses are lost. This T-cell lesion is specific to tumor-bearing hosts and not due to suppressor cells.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Tumor-specific cell-mediated immunity is crucial for controlling cancer.
- The Simian virus 40 (SV40)-induced mKSA tumor model allows study of tumor immunity in vivo.
- Assessing immune responses in tumor-bearing hosts is complex due to potential immune evasion mechanisms.
Purpose of the Study:
- To compare the sensitivity of four different assays in detecting tumor-specific cell-mediated immunity.
- To investigate the mechanisms behind the loss of immunity observed during tumor progression (the eclipse phenomenon).
- To characterize the nature of the immune defect in tumor-bearing hosts.
Main Methods:
- Comparison of Winn test, direct tumor challenge, microcytotoxicity assay, and 51-chromium-release lymphocytotoxicity assay.
- Monitoring tumor growth and immune status in syngeneic mice bearing mKSA tumors.
- Assessing T-cell function through graft-versus-host reactions and mitogen responses.
- Investigating the role of suppressor cells and serum factors in immune evasion.
Main Results:
- Major discrepancies were observed between the four assays in detecting cell-mediated immunity.
- The Winn test revealed progressive tumor growth and a subsequent loss of immunity (eclipse phenomenon).
- This eclipse phenomenon was identified as a specific T-cell system lesion in tumor-bearing hosts, independent of tumor location.
- Tumor-bearing animals maintained general T-cell functions like graft-versus-host reactions and mitogen responses.
- Immune cells from tumor-bearing mice could still recognize tumor antigens and reconstitute immunity.
- No suppressor cells or blocking serum factors were identified as the cause of the eclipse phenomenon.
Conclusions:
- The study highlights significant differences in detecting tumor immunity across various assays.
- A specific T-cell lesion, not attributable to suppressor cells, underlies the eclipse phenomenon during tumor growth.
- The findings suggest potential defects in T-cell precursors as a mechanism for immune evasion in cancer.