Further Characterization of Immunological Unresponsiveness Induced in Mice by Ultraviolet Radiation Growth and Induction of Nonultraviolet-Induced Tumors in Ultraviolet-Irradiated Mice

Kripke, Margaret L.; Thorn, Richard M.; Lill, Patsy H.; Civin, Curt I.; Pazmiño, Nelson H.; Fisher, Michael

doi:10.1097/00007890-197909000-00012

Cited by 52 publications

(16 citation statements)

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“…Murine UV-induced skin tumors are often immunogenic and accordingly rejected upon transplantation into immunocompetent hosts (9,10). These tumors grow only if the recipient animal is immunosuppressed by medication or chronic UV irradiation (11,12). Also, UV-induced suppressor T cells have been detected in UV-treated mice, which apparently promote tumor growth by suppressing antitumor effector functions (13).…”

mentioning

confidence: 99%

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

Loser

Scherer

Krummen

et al. 2005

The Journal of Immunology

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Although previous studies have shown that altered B7 costimulation plays a critical role in UV irradiation-induced regulation of immunity, the individual roles of the B7 receptors (CD28 and CTLA-4) or the B7 family members (CD80 and CD86) have not been explored. Thus, we investigated CTLA-4 signaling during photocarcinogenesis of chronically UV-B-exposed mice using an antagonistic anti-CTLA-4 Ab. Anti-CTLA-4-treated mice developed significantly fewer UV-induced tumors. Moreover, anti-CTLA-4 treatment induced long-lasting protective immunity because progressively growing UV tumors inoculated into anti-CTLA-4- and UV-treated mice that had not developed tumors were rejected. Next, we used mice deficient for CD80, CD86, or both in photocarcinogenesis studies to assess the relative contributions of these CTLA-4 ligands. Double-deficient mice showed significantly reduced UV-induced skin tumor development, whereas CD86−/− mice produced skin cancer earlier compared with CD80−/− and control mice. The growth of UV-induced tumors appears to be controlled by UV-induced suppressor T cells, because CD80−/−/CD86−/− mice had strongly reduced numbers of UV-induced CD4+CD25+ suppressor T cells. In vitro, CTLA-4 blockade inhibited the suppressor activity of UV-induced CD4+CD25+ T cells, suggesting that reduced photocarcinogenesis might be due to decreased numbers or function of suppressor T cells. Together, these data indicate that blocking CD80/86-CTLA-4 signaling induced immune protection against the development of UV-induced skin tumors. Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80.

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confidence: 99%

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

Loser

Scherer

Krummen

et al. 2005

The Journal of Immunology

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“…To date, few animal studies have explored the possible association between UV radiation and the development of lymphoid malignancies. One study found no effect of chronic UV irradiation on the incidence of leukemia in AKR strain mice, which develop a high incidence of leukemia early in life (10). A second study indicated that chronically UV-irradiated A strain mice developed leukemia at a very low frequency after a very long latent period (11).…”

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confidence: 99%

UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53

Jiang

Ananthaswamy

Muller

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen. p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL͞6 background, only one of the unirradiated mice lacking one copy of p53 (p53 ؉/؊ ) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53 ؉/؊ mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53 ؊/؊ ) rapidly developed thymic lymphomas and͞or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53 ؉/؊ mice, deletions in the p16 INK4a gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.tumor suppressor gene ͉ immune suppression T he incidence of non-Hodgkin's lymphoma (NHL) worldwide has increased substantially during the last two decades (1-3). This surge cannot be totally explained by the improvement in diagnosis and recording. Recently, epidemiological studies have suggested an association between the UV radiation in sunlight and the incidence of NHL (3-7). The rise in the incidence of NHL parallels the global increase in melanoma incidence, and patients with NHL are at higher risk of developing melanomas (4, 5). Studies from several groups have demonstrated an increased incidence of nonmelanoma skin cancers in persons with a history of NHL or chronic lymphocytic leukemia, and of NHL or chronic lymphocytic leukemia in persons with a history of skin cancers (5-7). UV radiation, especially...

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“…In hindsight, the tumors developed in UV-irradiated hosts were not edited. They further showed that prior exposure of recipient mice to subcarcinogenic doses of UV-B resulted in the acceptance of the transplanted tumors, clearly indicating that UV systemically suppresses host immunity against tumors (DeFabo & Kripke, 1979;Kripke, 1974). Tumors were accepted even when transplanted into sites not directly exposed to UV radiation, indicating that UV radiation exerts systemic immunosuppression (DeFabo & Kripke, 1979;.…”

Section: Uv Radiation Suppresses Anti-tumor Immunity and Promotes Tummentioning

confidence: 99%

“…Early work on UV-induced immunosuppression by Kripke and colleagues revealed that UV-B induced immunosuppression was transferable by adoptive transfer of lymphocytes from irradiated mice into non-irradiated mice Hostetler et al, 1989;Kripke & Fisher, 1976;Kripke et al, 1977;Kripke et al, 1979;Roberts et al, 1982;Spellman & Daynes, 1984;Ullrich & Kripke, 1984). In these studies, recipient mice infused with T cells from UV-irradiated mice were unable to reject UV-induced tumors Kripke & Fisher, 1976;Kripke et al, 1977;, but not non-UV-induced tumors such as tumors induced by chemical carcinogen (Hostetler et al, 1989;Kripke et al, 1979;Roberts et al, 1982;Spellman & Daynes, 1984;Ullrich & Kripke, 1984), suggesting some degree of antigen-specificity.…”

Section: Regulatory T Cells Are Responsible For the Uv-induced Supprementioning

confidence: 99%

“…In these studies, recipient mice infused with T cells from UV-irradiated mice were unable to reject UV-induced tumors Kripke & Fisher, 1976;Kripke et al, 1977;, but not non-UV-induced tumors such as tumors induced by chemical carcinogen (Hostetler et al, 1989;Kripke et al, 1979;Roberts et al, 1982;Spellman & Daynes, 1984;Ullrich & Kripke, 1984), suggesting some degree of antigen-specificity. Subsequent studies using a CHS model further delineated antigenspecific immune suppression by T cells from UV-irradiated hosts.…”

Section: Regulatory T Cells Are Responsible For the Uv-induced Supprementioning

confidence: 99%

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UV-Induced Immune Suppression that Promotes Skin Cancer Development and Progression

Kato¹,

Wang²

2011

Skin Cancers - Risk Factors, Prevention and Therapy

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Further Characterization of Immunological Unresponsiveness Induced in Mice by Ultraviolet Radiation Growth and Induction of Nonultraviolet-Induced Tumors in Ultraviolet-Irradiated Mice

Cited by 52 publications

References 0 publications

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53

UV-Induced Immune Suppression that Promotes Skin Cancer Development and Progression

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