PT  - JOURNAL ARTICLE
AU  - Fan Zhou
AU  - Justa Kardash
AU  - Hilal Bhat
AU  - Vikas Duhan
AU  - Sarah-Kim Friedrich
AU  - Judith Bezgovsek
AU  - Halime Kalkavan
AU  - Michael Bergerhausen
AU  - Max Schiller
AU  - Yara Machlah
AU  - Tim Brandenburg
AU  - Cornelia Hardt
AU  - Michal Krolik
AU  - Lukas Flatz
AU  - Philipp A. Lang
AU  - Karl S. Lang
TI  - Viral infection overcomes ineffectiveness of anti-tumoral CD8+ T cell mediated cytotoxicity
AID  - 10.1101/591198
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 591198
4099  - http://biorxiv.org/content/early/2019/03/27/591198.short
4100  - http://biorxiv.org/content/early/2019/03/27/591198.full
AB  - With the integration of PD-1 and CTLA-4 targeting immune checkpoint blockade into cancer treatment regimes, the anti-tumoral cytotoxicity of tumor-specific CD8+ T cells is well established. However, while the unresponsiveness of CD8+ T cells against big tumors is mainly explained by T cell exhaustion, other factors contributing to CD8+ T cell failure remain not well studied. Here we used a mouse melanoma model to study the interaction of growing tumor cells, innate immunity and CD8+ T cell responses induced by viral replication. Mouse model of melanoma (B16F10-OVA) and infections with arenaviruses. Growing B16F10-OVA cells did not induce systemic ablation of tumor specific CD8+ T cells. However, despite the presence of tumor-infiltrating CD8+ T cells, the anti-tumoral immune response was very limited. T cell anergy against the tumor was accompanied with a strong down-regulation of MHC-I on advanced tumors. LCMV infection restored the MHC class I expression, enhanced T cell function and lead to tumor regression. This study shows that tumor progression does not necessary lead to systemic exhaustion of the anti-tumoral CD8+ T cell response. Lack of innate signals is an additional reason for limited CD8+ T cell mediated cytotoxicity against the tumor.