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Utilization of influenza vaccination as an intratumoral immunotherapy for cancer
Descriptive
TitleInfo
Title
Utilization of influenza vaccination as an intratumoral immunotherapy for cancer
Name
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Newman
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Jenna
NamePart
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1993-
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Jenna Newman
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author
Name
(type = personal)
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Denzin
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Lisa
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Lisa Denzin
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Advisory Committee
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chair
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Rabson
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Arnold
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Arnold Rabson
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Advisory Committee
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internal member
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Covey
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Lori
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Lori Covey
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Advisory Committee
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outside member
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Rutgers University
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degree grantor
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School of Graduate Studies
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school
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Text
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theses
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2019
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2019-10
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2019
Language
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English
Abstract
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In recent years, immunotherapy for cancer has yielded unprecedented response rates and increased survival in patients. Despite progress, a significant fraction of patients exhibit progression of tumor growth during immunotherapy treatment. One barrier to response is the tumor microenvironment; patients who lack immune infiltration of their tumors or exhibit infiltration of suppressive cell subsets often do not respond to immunotherapy. In an effort to infiltrate the tumor microenvironment with pro-inflammatory cells (such as CD8+ T cells) that are correlated with response to immunotherapy in the clinic, inactivated influenza was administered intratumorally in immunocompetent mice. This vaccination slowed tumor growth when compared to that of mock-treated controls, and yielded an increased proportion in the tumor of dendritic cells, cross-presenting dendritic cells, CD8+ T cells, and tumor-reactive CD8+ T cells –all critical for anti-tumor immunity. Moreover, analysis of RNA from the vaccinated tumor revealed an upregulation in transcripts indicative of an inflamed tumor microenvironment, relative to that observed in mock-treated controls. Intratumoral influenza vaccination administered in combination with checkpoint blockade (αPD-L1) immunotherapy resulted in superior tumor control relative to that observed with either therapy alone. Further benefit derived from the intratumoral vaccination was protection from influenza infection. Interestingly, one vaccine formulation tested contained a squalene-based adjuvant; this vaccine did not slow tumor growth and failed to reduce the proportion of suppressive B regulatory cells (Bregs) in the tumor. Depletion of Bregs enabled the adjuvanted influenza vaccine to slow tumor growth. The research discussed in this dissertation indicates that intratumoral influenza vaccination may be used in the future as an immunotherapy for cancer; clinical trials are currently in preparation.
Subject
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Topic
Microbiology and Molecular Genetics
Subject
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Topic
Cancer -- Immunotherapy
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Rutgers University Electronic Theses and Dissertations
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ETD_10170
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1 online resource (xv, 121 pages) : illustrations
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Ph.D.
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Includes bibliographical references
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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NjNbRU
Identifier
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doi:10.7282/t3-0pcm-c323
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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Newman
GivenName
Jenna
Role
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Type
Permission or license
DateTime
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2019-08-15 23:49:56
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Jenna Newman
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Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2019-10-31
DateTime
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2021-10-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2021.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2019-09-14T15:03:15
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2019-09-14T15:03:15
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