Organ specificity of cancer metastasis depends on the adaptive immune surveillance and the neuronal chemokine fractalkine (TUM10P.1030)

• DOI: 10.4049/jimmunol.194.supp.211.11
• Publication Date: 2023-01-01T10:18:56Z
• Authors: Felix Nwajei; Figen Beceren-Braun; Konrad Gabrusiewicz; Meenakshi Shanmug...; Anna Zal; Wuenye Wu; Amy Heimberger
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Abstract The phenomenon of organ specificity in cancer metastasis has been traditionally interpreted in terms of the “seed and soil” hypothesis. However, the role of the adaptive immune system in this phenomenon is largely unknown and controversial. We found that MCA-fibrosarcoma cancer cells formed lethal tumors in the lungs, but not in the brain thereby representing a model of organ-specificity of cancer metastasis. Using this model, we assessed the role of the adaptive immune system. In immune competent multi-color fluorescent reporter mice, longitudinal intravital imaging via cranial windows revealed initial engraftment and growth of MCA cancer cells that was followed by tumor regression in concordance with T cell infiltration. However, MCA cancer cells formed lethal tumors in the brains of Rag1-KO mice indicating a key role for the adaptive immune system in the organ specificity of MCA cancer cell metastasis. In contrast, T cells were recruited to pulmonary MCA lesions but were ineffective in tumor rejection in that organ. Interestingly, T cell recruitment to MCA micrometastases in the brain was dramatically impeded in mice lacking the receptor for the neuronal chemokine fractalkine, and MCA tumors progressed in the brains of those mice. Our results reveal a role for brain-specific adaptive immunity to cancer metastasis and implicate fractalkine in regulating this process thereby broadening the “seed and soil” concept.