Long-Term Engraftment and Expansion of Tumor-Derived Memory T Cells Following the Implantation of Non-Disrupted Pieces of Human Lung Tumor into NOD-scid IL2R gamma super(null) Mice

• Published in: The Journal of immunology (1950) Vol. 180; no. 10; pp. 7009 - 7018
• Main Authors: Simpson-Abelson, Michelle R, Sonnenberg, Gregory F, Takita, Hiroshi, Yokota, Sandra J, Conway, Thomas FJr, Kelleher, Raymond JJr, Shultz, Leonard D, Barcos, Maurice, Bankert, Richard B
• Format: Journal Article
• Language: English
• Published: 01-05-2008
• ISSN: 0022-1767; 1550-6606

Non-disrupted pieces of primary human lung tumor implanted into NOD-scid IL2R gamma super(null) mice consistently result in successful xenografts in which tissue architecture, including tumor-associated leukocytes, stromal fibroblasts, and tumor cells are preserved for prolonged periods with limited host-vs-graft interference. Human CD45 super(+) tumor-associated leukocytes within the xenograft are predominantly CD3 super(+) T cells with fewer CD138 super(+) plasma cells. The effector memory T cells that had been shown to be quiescent in human lung tumor microenvironments can be activated in situ as determined by the production of human IFN- gamma in response to exogenous IL-12. Plasma cells remain functional as evidenced by production of human Ig. Significant levels of human IFN- gamma and Ig were detected in sera from xenograft-bearing mice for up to 9 wk postengraftment. Tumor-associated T cells were found to migrate from the microenvironment of the xenograft to the lung, liver, and primarily the spleen. At 8 wk postengraftment, a significant portion of cells isolated from the mouse spleens were found to be human CD45 super(+) cells. The majority of CD45 super(+) cells were CD3 super(+) and expressed a phenotype consistent with an effector memory T cell, consisting of CD4 super(+) or CD8 super(+) T cells that were CD45RO super(+), CD44 super(+), CD62L super(-), and CD25 super(-). Following adoptive transfer into non-tumor bearing NOD-scid IL2R gamma super(null) mice, these human T cells were found to expand in the spleen, produce IFN- gamma , and maintain an effector memory phenotype. We conclude that the NOD-scid IL2R gamma super(null) tumor xenograft model provides an opportunity to study tumor and tumor-stromal cell interactions in situ for prolonged periods.