Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

Frederick J. Kohlhapp, Erica J. Huelsmann, Andrew T. Lacek, Jason M. Schenkel, Jevgenijs Lusciks, Joseph R. Broucek, Josef W. Goldufsky, Tasha Hughes, Janet P. Zayas, Hubert Dolubizno, Ryan T. Sowell, Regina Kühner, Sarah Burd, John C. Kubasiak, Arman Nabatiyan, Sh'Rae Marshall, Praveen K. Bommareddy, Shengguo Li, Jenna H. Newman, Claude E. MonkenSasha H. Shafikhani, Amanda L. Marzo, Jose A. Guevara-Patino, Ahmed Lasfar, Paul G. Thomas, Edmund C. Lattime, Howard L. Kaufman, Andrew Zloza

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)957-965
Number of pages9
JournalCell Reports
Volume17
Issue number4
DOIs
StatePublished - Oct 18 2016
Externally publishedYes

Keywords

  • CD8 T cells
  • PD-1
  • breast cancer
  • cancer
  • concomitant
  • infection
  • influenza
  • melanoma
  • mouse
  • viral

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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