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Immunoselection of tumor cell variants by mice suppressed with ultraviolet radiation
Abstract:
It has previously been shown that mice exposed to ultraviolet radiation (UV) fail to reject highly immunogenic UV-induced tumors, which are regularly rejected by normal mice. The present study shows, however, that this immunosuppresion is incomplete, as UV-treated mice can still mount certain tumor-specific immune responses and reject smaller inocula of tumor cells that regularly grow progressively in athymic nude mice. Furthermore, all tumor cell lines that were reisolated from the tumor mass resulting from one tumor passage through UV-treated recipients heritably lost a tumor-specific determinant present on the parental tumor cells used for transplantation, and a large percentage of these reisolated variant tumors had changed to progressively growing tumors, in that they were no longer rejected by normal mice. In contrast, none of the tumors reisolated from passage through athymic nude mice or anti-idiotypically suppressed mice showed this change in antigenicity and progressive growth behavior. Thus, it appears that the phenotypic change in tumors reisolated from UV-treated mice was caused by immunoselection, and that the tumor-specific immunity in these mice apparently restrained the outgrowth of the parental tumor cells despite the partial immunosuppression. Because of the regularity at which tumor variants arose in the UV-treated mice after tumor transplantation, it appears that the partial immunosuppression caused by UV-treatment may have favored the outgrowth of antigenic variants from the parental tumor cell population, possibly by allowing more time for the generation of tumor variants. A similar immunoselection process might be part of tumor progression during tumor development and preferentially occur in cancer-bearing individuals showing concomitant tumor immunity.
Insights
Ultraviolet radiation (UV) exposure causes incomplete immunosuppression in mice, allowing some tumor-specific immunity. This partial immunity drives the selection of tumor variants that evade immune rejection, a process potentially relevant to human cancer progression.
Area of Science:
- Immunology
- Oncology
- Photobiology
Background:
- Mice exposed to ultraviolet radiation (UV) typically fail to reject UV-induced tumors.
- UV-induced immunosuppression is generally considered complete, preventing anti-tumor immune responses.
Purpose of the Study:
- To investigate the completeness of UV-induced immunosuppression in mice.
- To explore the mechanisms of tumor progression and immune evasion in UV-treated mice.
- To determine if tumor variants arise and are selected under partial immunosuppression.
Main Methods:
- Transplantation of UV-induced tumors into UV-treated mice and control groups (normal mice, athymic nude mice, anti-idiotypically suppressed mice).
- Analysis of tumor cell antigenicity and growth behavior after serial passage in different recipient mice.
- Assessment of tumor-specific immune responses in UV-treated mice.
Main Results:
- UV-treated mice exhibited incomplete immunosuppression, retaining some tumor-specific immunity.
- Tumor cell lines reisolated from UV-treated mice showed heritable loss of tumor-specific antigens and acquired progressive growth.
- Tumor variants with altered antigenicity and progressive growth were not observed in control groups, suggesting immunoselection in UV-treated mice.
- Partial immunosuppression in UV-treated mice appeared to favor the outgrowth of antigenic tumor variants.
Conclusions:
- UV-induced immunosuppression is incomplete and can lead to immunoselection of tumor variants.
- Tumor progression in UV-treated mice involves the selection of antigenically altered variants.
- This immunoselection process may contribute to tumor progression in cancer patients with concomitant tumor immunity.