Analysis of the influence of influenza virus infection on tumour progression and CD8+ T cell immunity

Currently, cancer is one of the leading causes of death worldwide and incidences continuously increase even further. Likewise, influenza A virus (IAV) infections are a substantial threat to global health. Although both diseases are highly studied individually, the interactions of immune responses towards cancer and infections are still not fully understood. Therefore, it is important to study the impact of infections on tumour development and the modulation of the tumour microenvironment, in order to derive new strategies for future therapies.

To investigate the mutual influence of IAV and cancer, B16 melanoma or CT26 colorectal cancer cells were subcutaneously transplanted into mice, which were then intranasally infected with IAV. Unlike expected, tumour growth was significantly slower upon IAV infection compared to non-infected mice, indicating a modulation of the anti-tumour response by the infection. Depletion of natural killer cells and macrophages demonstrated that these cells of the innate immune system are dispensable for the observed antitumoural effect whereas diminished inhibition of tumour growth correlated with CD8+ T cell depletion, indicating the importance of this population. Flow cytometric analysis indeed indicated that tumour-specific CD8+ T cells had an enhanced activation and proliferation phenotype upon IAV infection, as indicated by increased expression of the activation or proliferation markers CD43, granzyme B and Ki67. At the same time, inhibitory receptors reflecting T cell exhaustion were decreased on CD8+ T cells in tumours of infected mice compared to those of non-infected mice.

Subsequent analysis revealed, that the migration of those tumour-specific CD8+ T cells seems to be important. The adoptive cell transfer of congenically marked tumour-derived CD8+ T cells into recipient IAV infected tumour-bearing mice verified the migration of tumour derived CD8+ T cells into the tumour as well as into the infected lung, where a strong pro-inflammatory milieu prevailed. At the same time, this elevated migration of the transferred CD8+ T cells was not detectable in non-infected tumour-bearing mice. Further, the application of the lymphocyte egress inhibitor FTY720 demonstrated, that de novo infiltration of the tumour by CD8+ T cells is necessary for the IAV induced antitumoural effect.

In summary, this study shows what potentially protective influence an IAV infection can have during cancer by effectively enhancing the antitumour CD8+ T cell response.


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