Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis

Proteins involved in class I MHC (MHC-I) Ag processing, such as the TAP, ar e deficient in some human tumor cells. This suggests that antitumor respons es by CD8 T cells provide selection pressure to favor outgrowth of cells wi th defective processing of tumor Ags, Nonetheless, this evidence is only co rrelative, and controlled in vivo experiments have been lacking to demonstr ate that TAP deficiency promotes survival of tumor cells. To explore the ro le of Ag processing defects in tumor progression, matched panels of TAP1-po sitive and TAP1-negative tumor cell lines were generated from a parental tr ansformed murine fibroblast line, Inoculation of C57BL/6 mice with TAP1-neg ative cells produced large and persistent tumors. In contrast, TAP1-positiv e cells did not generate lasting tumors, although small tumors were detecte d transiently and regressed spontaneously. Both TAP1-positive and TAP1-nega tive cells produced tumors in athymic mice, confirming that TAP-dependent d ifferences in tumorigenicity were due to T cell-dependent immune responses. Inoculation of C57BL/6 mice with mixtures of TAP1-positive and TAP1-negati ve cells produced tumors composed exclusively of TAP1-negative cells, indic ating in vivo selection for cells with TAP deficiency. Thus, loss of TAP fu nction allows some tumor cells to avoid T cell-dependent elimination, resul ting in selection for tumor cells with deficient Ag processing.