Photoactivated 8‐methoxypsoralen treatment causes a peptide‐dependent increase in antigen display by transformed lymphocytes

Abstract Ex vivo exposure of malignant human T cells to photoactivated 8‐methoxypsoralen (8‐MOP a ), followed by their i.v. return, appears to vaccinate patients against tumor‐associated antigens of cutaneous T cell lymphoma in a procedure termed photopheresis. The molecular basis of this Food and Drug Administration‐approved therapy, administered in 100 centers worldwide, is unclear. Most of the attention to the mechanism of action of the drug has focused on its capacity to form covalent cross‐links with pyrimidine bases of DNA, thereby inhibiting cellular proliferation. Because immunologic factors appear to be important in the clinical response and could potentially serve as a model for immunotherapy of other malignancies, we explored the possibility that 8‐MOP‐treated cells display increased quantities of antigenic peptides at their cell surface. In this work, human B‐lymphoblastoid tissue culture lines were exposed to 8‐MOP a and expression of cell surface class I major histocompatibility complex proteins assessed, since CD8 T cells recognize antigenic moieties in the context of class I molecules. A peak 200–300% increase in MHC class I expression in 8‐MOP a ‐treated cells occurred at 20 hr. 8‐MOP a was far more effective in inducing this increase in class I MHC than other modalities, including mitomycin C, γ‐irradiation, ultraviolet B or heat or cold shock. This increase in surface class I MHC molecules appears to be driven by the degradation of cytoplasmic proteins into small peptides, followed by the transport of these peptides to MHC class I molecules in the endoplasmic reticulum. The data suggest that 8‐MOP a treatment may augment the immunogenicity of tumor and/or antigen‐presenting cells by enhancing processing and transport of class I MHC antigenic peptides. Int. J. Cancer 78:70–75, 1998.© 1998 Wiley‐Liss, Inc.