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At least 307 records · Page 17Linked to original sources
PubMed2004

UV radiation-induced immunosuppression and skin cancer.

UV radiation (UVR)-induced skin cancers in mice are highly antigenic and rejected by the host immune system when transplanted to syngeneic recipients. Exposure to UVB radiation causes immunologic changes that inhibit the host immune system from recognizing the tumor and leads to immunologic tolerance. This tolerance involves the appearance of regulatory T cells within the tumor-bearing hosts, which inhibit immunologic recognition of the tumor. Experiments performed with chemical haptens as surrogates for tumor antigens indicate that this comes about because of abnormal antigen presentation. Antigen-presenting cells (APCs) are prevented from performing their normal function by cytokines, most notably interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), released by keratinocytes and mast cells. Release of cytokines results from a cascade of UVR-induced events involving neuropeptides. Other immunosuppressive mediators released in the skin, as well as direct damage to Langerhans cells (LCs), are suspected of playing a role in UVR-induced immunosuppression. As a whole, data suggest a role for the immunologic effects of UVR in the pathogenesis of skin cancer.

Animals↗
PubMed2005

Perspectives on cancer therapy with radiolabeled monoclonal antibodies.

With the approval of 2 radiolabeled antibody products for the treatment of non-Hodgkin's lymphoma (NHL), radioimmunotherapy (RIT) has finally come of age as a new therapeutic modality, exemplifying the collaboration of multiple disciplines, including immunology, radiochemistry, radiation medicine, medical oncology, and nuclear medicine. Despite the many challenges that this new therapy discipline has encountered, there is growing evidence that RIT can have a significant impact on the treatment of cancer. Although follicular NHL is currently the only indication in which RIT has been proven to be effective, clinical trials are showing usefulness in other forms of NHL as well as in other hematologic neoplasms. However, the treatment of solid tumors remains a formidable challenge, because the doses shown to be effective in hematologic tumors are insufficient in the more common epithelial cancers. Nevertheless, there has been progress in locoregional applications and in the treatment of minimal residual disease. There is also optimism that pretargeting procedures, including new molecular constructs and targets, will improve the delivery of radioactivity to tumors, do so with less hematologic toxicity, and become the next generation of RIT.

Animals↗
PubMed2006

Advances in cancer therapy with radiolabeled monoclonal antibodies.

UNLABELLED: Two radiolabeled antibody products for the treatment of non-Hodgkin's lymphoma have been approved, thus indicating that cancer radioimmunotherapy (RAIT) has finally come of age as a new therapeutic modality, exemplifying the collaboration of multiple disciplines, including immunology, radiochemistry, radiation medicine, medical oncology, and nuclear medicine. Clinical trials are showing usefulness in other hematological neoplasms, but the treatment of solid tumors remains the major challenge, since the doses shown to be effective in hematological tumors are insufficient in the more common epithelial cancers. Nevertheless, use of RAIT in locoregional applications and in the treatment of minimal residual disease have shown promising RESULTS: There is also optimism that pretargeting procedures, including new molecular constructs and targets, will improve the delivery of radioactivity to tumors with less hematologic toxicity, and thus may become the next generation of RAIT.

Antibodies, Monoclonal↗
PubMed1996

Prevention of allogeneic marrow graft rejection by donor T cells that do not recognize recipient alloantigens: potential role of a veto mechanism.

Clinical trials and experimental studies have demonstrated that donor T cells can play a critical role in preventing allogeneic marrow graft rejection. Results of a previous study showed that donor T cells were most effective for preventing rejection when they recognize an alloantigen expressed by recipient T cells and can cause graft-versus-host disease (GVHD). The present study examined models where marrow graft rejection can be prevented by donor T cells that do not recognize host alloantigens and cannot cause GVHD. Donor T cells prevented rejection of major histocompatibility complex (MHC) class I and II-disparate F1 marrow in parental recipients prepared with > or = 800 cGy total body irradiation (TBI) but not in those prepared with < or = 750 cGy TBI. In recipients prepared with high TBI exposures, rejection was mediated entirely by host CD8 cells. With lower TBI exposures, rejection was mediated by host CD4 cells and CD8 cells. These observations suggested the hypothesis that donor T cells prevent rejection mediated by host effectors that recognize donor MHC class I alloantigens but do not prevent rejection mediated by host effectors that recognize donor class II alloantigens. Consistent with this hypothesis, further experiments showed that F1 donor T cells can prevent rejection of MHC class I-disparate marrow in irradiated parental recipients but have no detectable effect on rejection of MHC class II-disparate marrow. We propose that the expression of MHC class I molecules on donor T cells makes it possible for these cells to inactivate the host response against donor class I alloantigens through a veto mechanism, whereas the absence of MHC class II molecules on murine T cells explains why these cells cannot inactivate the host response against donor class II alloantigens. Finally, donor CD4 cells and CD8 cells were equivalently effective for preventing rejection of F1 marrow in parental recipients, suggesting that veto activity is not restricted solely to the CD8 subset of murine T cells. A veto mechanism could enable donor T cells to prevent allogeneic marrow graft rejection without causing GVHD.

Animals↗
PubMed1981

Differences in the immunologic reactivity of mice treated with UVB or methoxsalen plus UVA radiation.

Skin tumors induced in mice by chronic exposure to UVB radiation are often highly antigenic and regress when transplanted into normal syngeneic animals, but grow progressively in immunosuppressed mice. Exposure of mice to subtumorigenic doses of UVB radiation can abolish this immunologic rejection phenomenon. In this study, we have investigated the effects of treatment with 8-methoxypsoralen plus UVA radiation (PUVA) on the rejection of antigenic UVB-induced tumors. PUVA treatment, with either topical or systemic administration of the psoralen, did not alter the normal process of rejection of UVB-induced tumors. Mice treated with both minimally and markedly phototoxic doses of PUVA rejected tumors with a frequency similar to that seen in untreated animals, although these tumors grew progressively in UVB-irradiated mice. These results indicate that the effects of PUVA treatment differ from those of UVB irradiation in that PUVA treatment does not alter the immunologic rejection of UVB-induced tumors.

Animals↗
PubMed1995

[Distribution of haptoglobin types and their significance in biochemical and immunologic indicators in persons exposed to low radiation doses].

Haptoglobin (Hp) polymorphism and its significance for changes in biochemical and immunological parameters was analyzed in personnel of a nuclear plant receiving doses of external and internal irradiation close to maximum permissible levels. The distribution of Hp types and frequencies of alleles Hp in the group of probands asa a whole (1-1 - 14.1%; 2-1 - 49.2%; and 2-2 - 36.7%) and in probands subjected to different types and doses of irradiation (1-1, 13.6 - 16.0%; 2-1, 47.8 - 50.5%; and 2-2:35.8 - 38.2%) did not differ from those expected or from corresponding parameters of the control group and population. An increase in the frequency of allele Hp was observed for persons over 60 years of age. It was found that the levels of uric acid, the activities of acid phosphatase, lactate dehydrogenase, alkaline phosphatase and its isozymes, and the content of certain lymphocyte classes and immune complexes are initially higher in carriers of Hp type 1-1. In these probands, changes in certain parameters related to irradiation were observed less frequently. In some cases, opposite changes in immunological parameters were observed in persons with different Hp types after internal irradiation.

Acid Phosphatase↗
PubMed1977

Hydroxyanisole-induced regression of the Harding-Passey melanoma in mice.

The drug p-hydroxyanisole (OHA) was found to inhibit the incorporation of 3H-thymidine in the Harding-Passey melanoma cells in culture. Because the cultured cells had lost some of their pigment-forming capacity, the enzyme tyrosinase was added to the culture. This greatly increased the sensitivity of the cells to OHA, strongly suggesting that cells producing the enzyme would be preferentially killed by the drug. An in-vivo study of the effect of OHA injected into tumour-bearing mice showed a beneficial effect, including increased survival time, reduction in tumour size and in many cases complete loss of tumour and no recurrence. An experiment with animals immunologically suppressed by radiation suggests that the effect is not an immunological one.

Animals↗