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Pecking order among tumor-specific antigens
European Journal of Immunology
|February 1, 1984
Summary
Tumor cells can evade immune detection by losing specific antigens. This study reveals how fibrosarcoma 1591 tumor variants (1591-PRO) lose immunodominant antigens, allowing immune responses to target remaining immunorecessive antigens, facilitating immune escape.
Area of Science:
- Immunology
- Oncology
- Tumor immunology
Background:
- Ultraviolet light-induced fibrosarcoma 1591 is typically rejected in mice.
- Rarely, progressive variant tumors (1591-PRO) develop from this fibrosarcoma.
- These 1591-PRO tumors exhibit heritable stability.
Purpose of the Study:
- To induce transplantation resistance against 1591-PRO tumors.
- To identify antigens recognized by mice rejecting these progressor tumors.
- To understand the immune response to fibrosarcoma tumor antigens.
Main Methods:
- Inducing transplantation resistance to 1591-PRO tumors in syngeneic mice.
- Analyzing cytolytic T cell responses against tumor cells.
- Comparing antigen expression on parental (1591-RE) and variant (1591-PRO) tumors.
Main Results:
- A 1591-specific antigen recognized by T cells was present on both 1591-RE and 1591-PRO tumors.
- Immune responses rejecting 1591-RE lysed 1591-RE but not 1591-PRO cells.
- 1591-RE tumors expressed two tumor-specific antigens; 1591-PRO tumors lost one (immunodominant) but retained the other (immunorecessive).
Conclusions:
- A hierarchy of antigen recognition (immunodominance) exists for fibrosarcoma 1591.
- Loss of the immunodominant antigen allows the immune system to target the immunorecessive antigen.
- This antigen hierarchy and subsequent immune escape mechanism may explain tumor progression.