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Frederick Allen_Thesis.pdf (8.4 MB)

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CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular Trafficking and Interferon-Gamma Expression

Allen, Frederick, Jr.
http://rave.ohiolink.edu/etdc/view?acc_num=case1513124234665339

Abstract Details

2018, Doctor of Philosophy, Case Western Reserve University, Pathology.
Cancer evolves and thrives due to the failures of multiple intracellular and extracellular self-control mechanisms, and as such, often requires a multifaceted approach for complete eradication. An effective vaccine consists of specific, well-developed, and robust CD8+ T cell responses. However, while inducing tumor reactive CD8+ T cells in vitro or in vivo is achievable, the potential benefits often fail to translate into better patient outcomes. One of the major difficulties stems from the tumor's ability to induce immune tolerance. Studies have shown that immune cells can be induced to promote tumor growth or regression and chemokines are often integral organizers and modulators of these events. The ability for tumors to maintain a tolerant environment or for immunotherapy to promote strong long-lived antitumor CD8+ T cell responses is dependent on the tumor types and also the chemokines associated within the tumor milieu. Clinical data has shown that increased number of lymph nodes (LNs) infiltrated by tumors directly correlates with poor patient outcomes. Therefore, deciphering the complexities of immune interactions within LNs are essential to understanding how many tumors can redirect or suppress immune responses. Chemokines, such as CCL3, have the ability to attract naive CD8+ T cells and modulate their immune responses. CCL3 is also integral in orchestrating nonrandom naive CD8+ T cell contacts with dendritic cells (DCs) in the draining LNs (DLNs) of vaccinated mice9. These events lead to increased CD8+ T cell-DC surveillance time, decreases effector response time, and enhanced memory T cell generation; all of which are important in building an effective vaccine response. Furthermore, CCL3 has also been directly implicated in facilitating the clearance of some tumor models. These findings suggest possible therapeutic roles for CCL3 in redirecting tumor-tolerant milieus toward a tumor-immunogenic one by conditioning immune cells to induce an inflammatory response to tumor antigens (Ag). The body of work presented here discusses various dynamic cellular responses that occur during Ag capture, and subsequent early and late phase adaptive immune development in the tumor-DLN (TDLN) and at the primary tumor site (PTS) in response to CCL3 therapy.
Alex Huang (Advisor)
Pamela Wearsch (Committee Chair)
Pushpa Pandiyan (Committee Member)
Clive Hamlin (Committee Member)
178 p.
Immunology; Oncology
CCL3, Interferon-gamma, NK cells, Antigen presentation, Tumor, IFN, CD103 DC, dendritic cells, CXCL9, CXCL10

Recommended Citations

Citations

  • Allen, Jr., F. (2018). CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular Trafficking and Interferon-Gamma Expression [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1513124234665339

    APA Style (7th edition)

  • Allen, Jr., Frederick. CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular Trafficking and Interferon-Gamma Expression. 2018. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1513124234665339.

    MLA Style (8th edition)

  • Allen, Jr., Frederick. "CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular Trafficking and Interferon-Gamma Expression." Doctoral dissertation, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1513124234665339

    Chicago Manual of Style (17th edition)

case1513124234665339
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© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.