title: Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death.
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.
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kohlhapp
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Huelsmann
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lacek
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Jevgenijs
authors.initials: J
authors.lastname: Lusciks
authors.affiliation: Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Broucek
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Josef W
authors.initials: JW
authors.lastname: Goldufsky
authors.affiliation: Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Janet P
authors.initials: JP
authors.lastname: Zayas
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Hubert
authors.initials: H
authors.lastname: Dolubizno
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Sowell
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Kühner
authors.affiliation: University of Oxford, Oxford OX1 2JD, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Burd
authors.affiliation: Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kubasiak
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Nabatiyan
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Sh'Rae
authors.initials: S
authors.lastname: Marshall
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Bommareddy
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Shengguo
authors.initials: S
authors.lastname: Li
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Jenna H
authors.initials: JH
authors.lastname: Newman
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Claude E
authors.initials: CE
authors.lastname: Monken
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Sasha H
authors.initials: SH
authors.lastname: Shafikhani
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Marzo
authors.affiliation: Department of Surgery, Immunology Institute, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Guevara-Patino
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Lasfar
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Lattime
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.affiliation: Section of Surgical Oncology, Division of Surgical Oncology Research, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. Electronic address: andrew.zloza@rutgers.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D008168:Lung / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009857:Oncogenes; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism
chemical_list: D061026:Programmed Cell Death 1 Receptor
keywords: CD8(+) T cells; PD-1; breast cancer; cancer; concomitant; infection; influenza; melanoma; mouse; viral