Antigen expressed on tumor cells fails to elicit an immune response, even in the presence of increased numbers of tumor-specific cytotoxic T lymphocyte precursors

• Published in: Cancer research (Chicago, Ill.) Vol. 58; no. 17; pp. 3909 - 3917
• Main Authors: HERMANS, I. F, DAISH, A, JIANPING YANG, RITCHIE, D. S, RONCHESE, F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.1998
• Subjects: Adoptive Transfer; Animals; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Carcinoma, Lewis Lung - immunology; Dendritic Cells - immunology; Hematopoietic Stem Cells - immunology; Immunization; Immunotherapy; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Lung disease; Lewis lung carcinoma; Carcinoma; T cell receptor; Immune response; Tumor associated antigen; Respiratory disease; Spontaneous; Rodentia; Lymphocytic choriomeningitis; Cytokine; Malignant tumor; In vitro; Infection; In vivo; Vertebrata; Mammalia; Mouse; Viral disease; Animal; Immunotherapy; T-Lymphocyte; Tumor cell
• ISSN: 0008-5472; 1538-7445

We have used T-cell receptor (TCR) transgenic mice to analyze the interaction of tumors with the immune system. We show that the tumor cell line Lewis lung-lymphocytic choriomeningitis virus (LL-LCMV), genetically manipulated to express an H-2 Db-restricted epitope of the lymphocytic choriomeningitis virus glycoprotein (LCMV33-41), can grow progressively in TCR transgenic mice, where approximately 50% of CD8+ T cells are specific for LCMV33-41. TCR transgenic T cells were not deleted in tumor-bearing mice, and their surface phenotype and cytokine secretion patterns remained typical of naive T cells. Also, TCR transgenic T cells from tumor-bearing mice had undiminished capacity to proliferate to antigen in vitro. Tumor-protective immune responses could be elicited in TCR transgenic mice by immunization with LCMV33-41 peptide-loaded dendritic cells. Tumor resistance correlated with the switch of TCR transgenic T cells from a CD44low to a CD44high phenotype and increased capacity to produce IFNgamma in vitro. Results similar to those obtained in TCR transgenic mice were also obtained using an adoptive transfer system, where small numbers of TCR transgenic T cells were injected into normal C57BL/6 hosts. These data indicate that even large tumors may not induce specific immunization, tolerance, or anergy to tumor antigens, and that high numbers of tumor-specific CTL precursors are not sufficient to provide tumor resistance.