The CX3CL1-CX3CR1 chemokine axis can contribute to tumor immune evasion and blockade with a novel CX3CR1 monoclonal antibody enhances response to anti-PD-1 immunotherapy

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing critical role metastasis of CX3CR1 expressing cancer cells. can be expressed both and immune-inhibitory myeloid cells to facilitate their migration. We generated novel monoclonal antibody against mouse that binds blocks CX3CL1-CX3CR1 interaction. next explored immune evasion strategies implemented by axis find it initiates resistance program results 1) facilitation cell migration, 2) secretion soluble mediators generate pro-metastatic niche, 3) attract populations, 4) generation tumor-inflammasome. The reduces migration decreases suppressive In combination with anti-PD-1 immunotherapy, this enhances survival an immunocompetent colon carcinoma model through decrease tumor-promoting populations. Thus, is involved mechanisms immunotherapy therapy overcome portion anti-PD-1.