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Increase in Immunogenicity and Sensitivity to Natural Cell-mediated Cytotoxicity following in Vitro Exposure of MCA105 Tumor Cells to Ultraviolet Radiation

Mirsada Begovi¹, Ronald Herberman and Elieser Gorelik²

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

The effect of short wave length ultraviolet C (UVC) light irradiation on tumor cell immunogenicity and sensitivity to natural cell-mediated cytotoxicity was studied. Two consecutive courses of UVC irradiation of 3LL Lewis lung carcinoma and MCA105 fibrosarcoma increased their immunogenicity and sensitivity to lysis by normal spleen cells. Analysis of the effector cells involved in lysis of the parental MCA105 and UV-treated MCA105UV tumor cells was performed by comparing the cytotoxic activity of normal spleen cells containing both natural killer (NK) and natural cytotoxicity (NC) cell activity (NK+, NC+) with: (a) normal spleen cells in which NC activity was neutralized by anti-tumor necrosis factor (TNF) antibodies (NK+, NC-); (b) NK-depleted or NK-deficient spleen cells (NK-, NC+); and (c) NK-depleted or -deficient spleen cells with NC activity blocked by anti-TNF antibodies (NK-, NC-). In addition, the ability of polyinosinic-polycytidylic acid or interleukin 2-stimulated spleen cells to lyse UV-treated and untreated tumor cells in the presence or absence of anti-TNF antibodies was also investigated. Lysis of MCA105 cells was shown to be mediated mostly by NC cells, since it was inhibited in the presence of anti-TNF antibodies and was not significantly affected by depletion or stimulation of NK cells. UV irradiation of MCA105 tumor cells substantially increased their sensitivity to both NK and NC effector cells. Augmentation of NK sensitivity of MCA105UV cells was associated with an increase in their lysability by large granular lymphocyte-derived cytolytic granules. UVC treatment of tumor cells also increased their sensitivity to lysis by recombinant TNF-, pointing to the possible mechanism responsible for the increase in their sensitivity to NC cell-mediated cytotoxicity. Indeed, selection of MCA105UV cells for resistance to TNF led to resistance to spleen cell-mediated NC cytotoxicity. UVC irradiation did not affect internalization and degradation of TNF by MCA105UV cells but substantially increased sensitivity to TNF-induced DNA fragmentation. The results of this study indicate that UV irradiation can be a potent and stable modulator of the immunobiological properties of tumor cells.

¹ Present address: Institute of Radiology and Oncology, University Medical Center, 25 Mose Pijade, Sarajevo 71000, Yugoslavia.

² To whom requests for reprints should be addressed, at Pittsburgh Cancer Institute, Biomedical Science Tower, Room W954, DeSoto & O'Hara Street, Pittsburgh, PA 15213.

Received 3/27/91. Accepted 7/19/91.