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Effect of Ultraviolet Irradiation on MCA102 Tumor Cell Immunogenicity and Sensitivity to Tumor Necrosis Factor

Elieser Gorelik¹, Mirsada Begovi², Lisa Duty and Ronald B. Herberman

Pittsburgh Cancer Institute and Departments of Pathology and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

The ability of UV irradiation to induce immunogenicity of the nonimmunogenic major histocompatibility complex-negative MCA102 fibrosarcoma was studied. In parallel, the effect of short wavelength UVC light on the sensitivity of tumor cells to natural cell-mediated cytotoxicity and tumor necrosis factor (TNF) was also investigated. MCA102 fibrosarcoma cells were irradiated in vitro twice with UVC light (610 and 457 J/m²). Surviving cells were expanded and maintained in vitro as the MCA102UV subline. UV treatment changed tumor cell morphology and increased their in vitro rate of proliferation. However, after inoculation of 1 x 10⁵ to 2 x 10⁶ MCA102UV cells into C57BL/6 mice, growth of these cells was completely prevented. Lyt2.2 and not L3T4 lymphocytes were responsible for the rejection of these tumor cells. To determine the minimal and optimal dose of UV irradiation capable of increasing tumor cell immunogenicity, MCA102 cells were irradiated once or twice with different doses (76 to 610 J/m²) of UV light. After a single dose of UV treatment, tumor growth in C57BL/6 mice was inhibited, particularly with lines irradiated at the highest doses (610 or 457 J/m²). After a second round of irradiation, tumor cells became more immunogenic, and the level of tumor growth inhibition increased with higher doses of UV irradiation. Thus, cells irradiated twice with 610 and 457 J/m² became rejectable in all immunocompetent C57BL/6 mice. The increase in tumor cell immunogenicity induced by UV light was not associated with the appearance of Class I H-2 antigens. In parallel with the induction of tumor cell immunogenicity, UV irradiation made tumor cells more sensitive to natural cell-mediated cytotoxicity and to lysis by TNF. An increase in sensitivity to natural cell-mediated cytotoxicity and TNF was observed after single or double doses (152 to 610 J/m²) of UV irradiation. The cells that showed the highest levels of immunogenicity were found also to be most sensitive to lysis by TNF. MCA102UV cells cultured in the presence of increased doses of recombinant TNF became resistant to its cytotoxicity without losing their immunogenicity, suggesting that immunogenicity and TNF sensitivity are two independent UV-induced properties. Thus, UV irradiation appears to be an effective modality for altering tumor cell immunobiological properties, including increased tumor cell sensitivity to T-cell and/or natural cell-mediated immunity.

¹ To whom requests for reprints should be addressed, at Pittsburgh Cancer Institute, 3343 Forbes Avenue, Pittsburgh, PA 15213.

² Present address: Institute of Radiology and Oncology, University Medical Center, 25 Mose Pijade, Sarajevo 71000, Yugoslavia.

Received 8/20/90. Accepted 12/19/90.