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. Monken; Sasha H. Shafikhani; Amanda L. Marzo; Jose A. Guevara-Patino; Ahmed Lasfar; Paul G. Thomas; Edmund C. Lattime; Howard L. Kaufman; Andrew Zloza

doi:10.1016/j.celrep.2016.09.068

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 journal › Article › peer-review

21 Scopus citations

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 language	English (US)
Pages (from-to)	957-965
Number of pages	9
Journal	Cell Reports
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2016.09.068
State	Published - Oct 18 2016
Externally published	Yes

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

Access to Document

10.1016/j.celrep.2016.09.068

Cite this

Kohlhapp, F. J., Huelsmann, E. J., Lacek, A. T., Schenkel, J. M., Lusciks, J., Broucek, J. R., Goldufsky, J. W., Hughes, T., Zayas, J. P., Dolubizno, H., Sowell, R. T., Kühner, R., Burd, S., Kubasiak, J. C., Nabatiyan, A., Marshall, SR., Bommareddy, P. K., Li, S., Newman, J. H., ... Zloza, A. (2016). Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death. Cell Reports, 17(4), 957-965. https://doi.org/10.1016/j.celrep.2016.09.068

Kohlhapp, FJ, Huelsmann, EJ, Lacek, AT, Schenkel, JM, Lusciks, J, Broucek, JR, Goldufsky, JW, Hughes, T, Zayas, JP, Dolubizno, H, Sowell, RT, Kühner, R, Burd, S, Kubasiak, JC, Nabatiyan, A, Marshall, SR, Bommareddy, PK, Li, S, Newman, JH, Monken, CE, Shafikhani, SH, Marzo, AL, Guevara-Patino, JA, Lasfar, A, Thomas, PG, Lattime, EC, Kaufman, HL & Zloza, A 2016, 'Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death', Cell Reports, vol. 17, no. 4, pp. 957-965. https://doi.org/10.1016/j.celrep.2016.09.068

@article{57b0f61a5df645688d25cd5eaa980d81,

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.",

keywords = "CD8 T cells, PD-1, breast cancer, cancer, concomitant, infection, influenza, melanoma, mouse, viral",

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

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s)",

year = "2016",

month = oct,

day = "18",

doi = "10.1016/j.celrep.2016.09.068",

language = "English (US)",

volume = "17",

pages = "957--965",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

AU - Kohlhapp, Frederick J.

AU - Huelsmann, Erica J.

AU - Lacek, Andrew T.

AU - Schenkel, Jason M.

AU - Lusciks, Jevgenijs

AU - Broucek, Joseph R.

AU - Goldufsky, Josef W.

AU - Hughes, Tasha

AU - Zayas, Janet P.

AU - Dolubizno, Hubert

AU - Sowell, Ryan T.

AU - Kühner, Regina

AU - Burd, Sarah

AU - Kubasiak, John C.

AU - Nabatiyan, Arman

AU - Marshall, Sh'Rae

AU - Bommareddy, Praveen K.

AU - Li, Shengguo

AU - Newman, Jenna H.

AU - Monken, Claude E.

AU - Shafikhani, Sasha H.

AU - Marzo, Amanda L.

AU - Guevara-Patino, Jose A.

AU - Lasfar, Ahmed

AU - Thomas, Paul G.

AU - Lattime, Edmund C.

AU - Kaufman, Howard L.

AU - Zloza, Andrew

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - PD-1

KW - breast cancer

KW - cancer

KW - concomitant

KW - infection

KW - influenza

KW - melanoma

KW - mouse

KW - viral

UR - http://www.scopus.com/inward/record.url?scp=84994893508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994893508&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.09.068

DO - 10.1016/j.celrep.2016.09.068

M3 - Article

C2 - 27760326

AN - SCOPUS:84994893508

SN - 2211-1247

VL - 17

SP - 957

EP - 965

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this