Abstract 1902: A multilevel map of the immunological terrain in an orthotopic mouse model of lung cancer with emphasis on PGD2/DP1-dependent immunomodulation

Abstract

Abstract The influence of the organ-specific micro-environment on the host immune response to tumors has been insufficiently adressed. We examined tumor-induced immunomodulation in an orthotopic mouse model of lung cancer. We focused on the PGD2-DP1 signalling axis given its contrasting roles in dendritic cell (DC)-dependent immunomodulation on one hand, and tumor angiogenesis on the other. We found an enrichment of CD11b+ (inflammatory type) DCs within lung tumors. In sharp contrast to DCs in immediately adjacent peritumoral lung tissue, intratumoral DCs displayed a strong upregulation of the T-cell co-inhibitory molecules PD-L1 and ICOS-L on the cell surface. Remarkably, tumor-infiltrating CD4 and CD8 T-cells showed a robust upregulation of the activation marker CD69, while increased numbers of double-negative T-cells were seen within lung tumors as well. Regulatory T-cells were also clearly elevated within tumors as well as in draining lymph nodes (LN) of tumor-bearing hosts. Interestingly, DCs in lung-draining LNs appeared more immature in end-stage tumor bearing mice. Finally, systemic tumor-induced effects were manifest as a strong expansion of myeloid derived suppressor cells in the spleen. DP1-deficiency did not significantly affect any of these immunological parameters. Moreover, in contrast to previous observations using heterotopically implanted lung tumor cells, DP1-deficiency had no impact on survival in our orthotopic lung cancer model. In summary, we provide a multi-level detailed map of tumor-immune system interactions in an orthotopic mouse model of lung cancer. Our findings in DP1-deficient mice stress the importance of the local, organ-specific milieu in driving tumor development and shaping host immune responses. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1902.