HUMAN SUNLIGHT-INDUCED BASAL-CELL-CARCINOMA-ASSOCIATED DENDRITIC CELLS ARE DEFICIENT IN T-CELL COSTIMULATORY MOLECULES AND ARE IMPAIRED AS ANTIGEN-PRESENTING CELLS

Immune surveillance of skin cancer involves the stimulation of effecto r T cells by tumor-derived antigens and antigen-presenting cells (APCs ), An effective APC must not only display processed antigen in the con text of MHC molecules but also express co-stimulatory molecules that a re required to fully activate T cells, One of the most common cutaneou s neoplasms Is basal cell car cinoma. To investigate expression of he co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor-associat ed dendritic cells (TADCs), cryosections from basal cell carcinomas we re immunostained. In basal cell carcinomas, only I to 2% of intratumor and 5 to 10% of peritumor APCs expressed CD80 or CD86. In contrast, b iopsies of immunological/inflammatory dermatoses revealed that 38 to 7 3% of APCs expressed CD80 and CD86. To further evaluate their phenotyp e and function, TADCs were isolated from tissue samples of basal cell carcinomas; they were nonadherent to plastic, displayed a typical dend ritic morphology, and expressed high levels of major histocompatibilit y class II molecules on their surface When TADCs were compared with de ntritic cells from blood for presentation of superantigens (staphyloco ccal enterotoxins A and B) to resting autologous T cells, TADCs were c onsistently weaker stimulators of T cell proliferation than blood dend ritic cells, When analyzed by flow cytometry, TADCs expressed high lev els of HLA-DR, but only 5 to 10% co-expressed CD80 or CD86. A 3-day cu lture in granulocyte/macrophage colony-stimulating factor-containing m edium partially reconstituted the TADC expression of CD80 and CD86 as well as their immunostimulatory capacity Thus, in this common skin can cer, although there are prominent collections of HLA-DR-positive APCs in and around tumor cells, the TADCs are deficient in important co-sti mulatory molecules as well as being weak stimulators of T cell prolife ration, The paucity of co-stimulatory molecule expression and function al activity of TADCs may explain why the local T lymphocytic infiltrat e fails to become fully activated to eradicate adjacent tumor cells, F rom a clinical perspective, these findings suggest a novel immunothera peutic strategy targeting T cell co-stimulatory molecules on professio nal APCs in cutaneous oncology.