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Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death.
- Kohlhapp, Frederick;
- Huelsmann, Erica;
- Lacek, Andrew;
- Schenkel, Jason;
- Lusciks, Jevgenijs;
- Broucek, Joseph;
- Goldufsky, Josef;
- Hughes, Tasha;
- Zayas, Janet;
- Dolubizno, Hubert;
- Sowell, Ryan;
- Kühner, Regina;
- Burd, Sarah;
- Kubasiak, John;
- Nabatiyan, Arman;
- Marshall, ShRae;
- Bommareddy, Praveen;
- Li, Shengguo;
- Newman, Jenna;
- Monken, Claude;
- Shafikhani, Sasha;
- Marzo, Amanda;
- Guevara-Patino, Jose;
- Lasfar, Ahmed;
- Thomas, Paul;
- Lattime, Edmund;
- Kaufman, Howard;
- Zloza, Andrew
- et al.
Published Web Location
https://doi.org/10.1016/j.celrep.2016.09.068Abstract
In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1). Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.
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