Related Experiment Videos
Pecking order among tumor-specific antigens
Abstract:
The ultraviolet light-induced fibrosarcoma 1591 is regularly rejected upon transplantation into young syngeneic mice; in rare instances, however, this tumor grows progressively and the tumors that develop are then heritably stable variant progressor tumors (1591-PRO tumors). In this study, we have induced transplantation resistance to 1591-PRO tumors and determined which antigens were recognized by mice that rejected these progressor tumors. We found that cytolytic T cells of such mice recognized a 1591-specific antigen that was present not only on all the independently derived 1591-PRO tumors but also on the parental regressor tumor (1591-RE). However, the cytolytic immune response of mice that rejected 1591-RE lysed 1591-RE tumor cells but not 1591-PRO tumor cells. Thus, the 1591-RE tumor seemed to express two antigens that were specific for tumors of the 1591 lineage, one that was lost and a second that was retained by 1591-PRO tumor cells. Mice challenged with 1591-R# tumor cells mounted a response to only one of the tumor-specific antigens which was therefore "immunodominant" over the other "immunorecessive" antigen. This immunorecessive antigen became the target of the immune response once the immunodominant antigen was lost. This "pecking order" interfered with the simultaneous recognition of two tumor-specific antigens and this mechanism may favor immune escape.
Insights
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.