Increasing Tumor Antigen Expression Overcomes “Ignorance” to Solid Tumors via Crosspresentation by Bone Marrow-Derived Stromal Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 17; no. 6; pp. 737 - 747
• Main Authors: Spiotto, Michael T., Yu, Ping, Rowley, Donald A., Nishimura, Michael I., Meredith, Stephen C., Gajewski, Thomas F., Fu, Yang-Xin, Schreiber, Hans
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2002; Elsevier Limited
• Subjects: Animals; Antigen Presentation - immunology; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Bone Marrow Cells - immunology; Cancer; Cell culture; Cloning; Colleges & universities; Cytotoxicity, Immunologic; Dilution; Genes; Grants; Lymphocytes; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms, Experimental - immunology; Rodents; Stromal Cells - immunology; Transgenic animals; Tumor Escape; Tumors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(02)00480-6

To explain why solid cancers grow or are rejected, we examined how the tumor stroma affected the level of antigen expression necessary to induce an immune response. We applied a tamoxifen-regulated Cre-loxP system to induce a model SIYRYYGL antigen recognized by the 2C T cell receptor. Solid tumors expressing the antigen at lower levels grew, whereas solid tumors expressing antigen induced to 26-fold higher levels were rejected. In contrast, mice rejected cell suspensions expressing higher or lower levels of the antigen. The antigen was likely crosspresented because draining lymph node responses required bone marrow-derived cells in the tumor stroma. Thus, tumor antigens expressed at levels sufficient for crosspresentation by bone marrow-derived stromal cells may overcome immunological “ignorance” to solid tumors.