Author ORCID Identifier


Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation


Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Dr. Gregory Lizee

Committee Member

Dr. Patrick Hwu

Committee Member

Dr. Gordon Freeman

Committee Member

Dr. Sharon Dent

Committee Member

Dr. Michael Davies

Committee Member

Dr. Kunal Rai


CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract myeloid populations, and 4) generation of tumor-inflammasome. This axis is involved in the underlying mechanisms of resistance to anti-PD-1 immunotherapy. We used a novel monoclonal antibody against mouse CX3CR1 that binds to CX3CR1, blocks the CX3CL1-CX3CR1 interaction and antagonizes the pro-tumorigenic outcome of this axis. This monoclonal antibody reduces migration of tumor cells and decreases secretion of immune suppressive soluble mediators from the tumor. In combination with anti-PD-1 immunotherapy, this CX3CR1 monoclonal antibody enhances survival in an immunocompetent mouse colon carcinoma model through a decrease in tumor-associated myeloid populations and their conversion into an anti-tumor phenotype.


CX3CR1, CX3CL1, PD-1, tumor immune evasion, cancer immunotherapy



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