P201
Respiratory but not systemic viral infection induces tumour growth inhibition through CD8+ T-cell activation.
STEINBACH P. 1, SUTTER K. 2, WESTENDORF A. 1, BUER J. 1, KNUSCHKE T. 1
1 Institute of Medical Microbiology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany; 2 Institute for Virology, University of Duisburg-Essen, University Hospital Essen, Germany, Essen, Germany
The mucosa of the lung has unique immunological characteristics that contribute to the regulation of an immune response. So far, it is not well studied how a lung infection affects distal immune reactions. Here, we studied the impact of viral lung infection on the immunological control of tumours.
For this purpose, we used different preclinical mouse models of cancer. Tumours (B16, CT26 or LLC) were subcutaneously transplanted into mice, which were then infected with influenza A virus (IAV). Interestingly, tumour growth was significantly decreased after IAV infection compared to non-infected mice, pointing towards a modulation of the anti-tumour immune response by the infection. Tumour-specific CD8+ T-cells appear to be recruited to the inflamed lung - where they experience strong activation - since we could detect them in both organs, tumour and lung. This effect was consistent in different tumour models and mouse strains. The importance of migrating CD8+ T-cells in this model is supported by the observation that the depletion of CD8+ T-cells as well as inhibition of lymphocyte egression by FTY720 reversed the effect of tumour growth inhibition. In contrast, systemic retroviral infection did not have a comparably strong impact on tumour-specific CD8+ T-cell responses, resulting in enhanced tumour growth compared to IAV- or non-infected mice. At the same time, we could detect increased amounts of regulatory T-cells, which could have a significant impact on the restriction of tumour-specific CD8+ T-cells. Altogether, we could show that although locally apart, respiratory infection clearly affects distal tumour immunology – in contrast to a systemic infection. Hence, the mucosal environment of the inflamed lung seems to be important for the observed tumour growth delay.
Our results will help to understand the mechanisms of how infections modulate the control of cancers and will advance our understanding of the cross-talk between cancer and infections.
For this purpose, we used different preclinical mouse models of cancer. Tumours (B16, CT26 or LLC) were subcutaneously transplanted into mice, which were then infected with influenza A virus (IAV). Interestingly, tumour growth was significantly decreased after IAV infection compared to non-infected mice, pointing towards a modulation of the anti-tumour immune response by the infection. Tumour-specific CD8+ T-cells appear to be recruited to the inflamed lung - where they experience strong activation - since we could detect them in both organs, tumour and lung. This effect was consistent in different tumour models and mouse strains. The importance of migrating CD8+ T-cells in this model is supported by the observation that the depletion of CD8+ T-cells as well as inhibition of lymphocyte egression by FTY720 reversed the effect of tumour growth inhibition. In contrast, systemic retroviral infection did not have a comparably strong impact on tumour-specific CD8+ T-cell responses, resulting in enhanced tumour growth compared to IAV- or non-infected mice. At the same time, we could detect increased amounts of regulatory T-cells, which could have a significant impact on the restriction of tumour-specific CD8+ T-cells. Altogether, we could show that although locally apart, respiratory infection clearly affects distal tumour immunology – in contrast to a systemic infection. Hence, the mucosal environment of the inflamed lung seems to be important for the observed tumour growth delay.
Our results will help to understand the mechanisms of how infections modulate the control of cancers and will advance our understanding of the cross-talk between cancer and infections.