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Shared T cell-defined antigens on independently derived tumors
D M Sahasrabudhe1, D Burstyn, J C Dusel
1Cancer Center, University of Rochester School of Medicine and Dentistry, NY 14642.
Abstract:
We report that a subset of tumors independently derived from a cloned line of contact-inhibited, non-tumorigenic murine fetal fibroblasts confer cross-protective immunity against each other in vivo. Concordant with the in vivo cross-protection, cytolytic T cell clones from mice immunized with one of these tumor lines specifically lyse the three other lines in the same set but do not cross-react with either the nontumorigenic parental line or another similarly derived tumor line representing a different antigenic profile. This and other recent evidence for shared expression of tumor rejection Ag contrasts with the antigenic diversity previously described for chemical- and radiation-induced tumors. In the interpretation of such data it is essential to distinguish between Ag expressed in association with the transformation process and Ag induced by random mutation of already transformed cells.
Insights
Tumors from cloned cells can provide cross-protective immunity in mice. Cytolytic T cells recognize shared tumor rejection antigens, contrasting with diverse tumor profiles.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Tumor-specific antigens (TSAs) are crucial for cancer immunotherapy.
- Understanding the antigenic profile of tumors is essential for developing effective cancer vaccines.
- Previous studies indicated significant antigenic diversity in chemically or radiation-induced tumors.
Purpose of the Study:
- To investigate cross-protective immunity among tumors derived from a cloned cell line.
- To characterize the antigenic profile of these independently derived tumors.
- To determine if shared tumor rejection antigens are expressed.
Main Methods:
- Independently derived tumor lines from cloned murine fetal fibroblasts.
- In vivo immunization and challenge experiments.
- Generation and characterization of cytolytic T cell clones.
- In vitro tumor cell lysis assays.
Main Results:
- A subset of independently derived tumors conferred cross-protective immunity in vivo.
- Cytolytic T cell clones specifically lysed tumor lines sharing antigenic profiles.
- No cross-reactivity was observed with the parental non-tumorigenic cell line.
- These findings suggest shared expression of tumor rejection antigens.
Conclusions:
- Tumors derived from a cloned cell line can express shared tumor rejection antigens.
- This shared antigenicity can elicit cross-protective immunity.
- Distinguishing between transformation-associated antigens and mutation-induced antigens is critical for interpreting tumor immunology data.