CX3CL1 as potential immunotherapeutic tool for bone metastases in lung cancer: A preclinical study

The chemokine CX3CL1 emerges as a double-edged sword in the pathophysiology of cancer. We investigated whether CX3CL1 would act as an impediment or as a support to the development of non-small cell lung cancer skeletal metastases.We set up an in vivo experimental skeletal metastasis model using the LL2 lung cancer cell line expressing low or high levels of CX3CL1. The resulting bone tumors were analyzed using histological, flow cytometry and transcriptomic techniques.The increased CX3CL1 expression was associated with a strong anti-tumor effect. We observed a significant reduced tumor burden in the high-CX3CL1 group compared to the low-CX3CL1 group with significant differences in the composition of the tumor-infiltrating leukocytes and immunity- and osteogenesis-related gene expression.Our results highlight the CX3CL1 ability to reduce cancer cell tumorigenicity by potentially disrupting both the vicious cycle linking bone resorption and the tumor cell proliferation as well as by generating an immune permissive tumor microenvironment rich in cancer-fighting immune cells, especially M1 monocytes, B cells and NK cells. In that regard, CX3CL1 could be an interesting tool to increase and/or predict the success of immune-based therapies requiring immune cell trafficking.