Impact of non-oncogenic acute viral infection on anti-tumor CD8+ T cell responses (TUM5P.938)

Abstract

Abstract Background: Factors dictating clinical emergence of cancer are not fully understood. Specifically, how non-oncogenic acute viral infections affect unrelated anti-tumor CD8+ T cell responses (those in uninfected tissues) is unknown. Methods: Therefore, we infected B6 mice with non-lethal Influenza (A/PR/8-OVA, 80,000 EID50, intranasally) 3 days prior to challenge with B16-F10 melanoma (120,000 cells, subcutaneously, right flank). To track self/tumor antigen, virus-expressing antigen, and unrelated foreign antigen CD8+ T cells, we transferred pmel (gp100-specific, Thy1.1+Ly5.1-), OT-I (OVA-specific, Thy1.1+Ly5.1+), and P14 (LCMV gp33, Thy1.1-Ly5.1-) CD8+ T cells, respectively, into Thy1.1-Ly5.1+ B6 mice. Results: Influenza infection significantly worsened normal host anti-tumor responses and decreased host survival with cancer from ~32 to ~15 days (P<0.01). Interestingly, pmel (but not OT-I and P14) CD8+ T cells circulating to the infected lung underwent cell death resulting in their eventual loss from the tumor microenvironment (up to 90%; P<0.001). Similar findings were observed with infections 15 or 30 days before or 7 days after B16 challenge and when Balb/c or humanized NSG mice were challenged with breast cancer or melanoma in the context of LCMV or HIV. Conclusions: Our findings may explain the clinical phenomenon emerging from epidemiologic studies reporting increased unrelated cancer in patients with non-oncogenic viral infections.