Long-range Deployment of Tumor-antigen Specific Cytotoxic T Lymphocytes Inhibits Lung Metastasis of Breast Cancer

Immune checkpoint blockade (ICB) has imported tremendous success in cancer therapy by reactivating effector immune cells. Patients exhibiting immune-hot or “inflamed” phenotype, characterized by extensive infiltration of effector immune cells, are usually beneficial from ICB. However, primary tumors could collaborate with the infiltrated inflammatory cells to profoundly dampen local infiltration of effector T cells, leading to an immune-cold phenotype that does not respond to ICB. Recently, we proposed that systemic deployment of effector T cells (Effector Immune Cell Deployment, EICD) is crucial in immunosurveillance, while defective EICD may result an immune-cold phenotype in cancer patients causing cancer immune evasion(Zhang et al., 2022a). It has been noted that changes in the inflammatory microenvironment of distant organs may have significant impacts on pre-metastatic immune remodeling, leading to infiltration of pro-tumoral (Kaplan et al., 2005) or anti-tumoral innate immune cells in the pre-metastatic niche(Hanna et al., 2015). These contradictory evidences presented double-edged effects of innate immune response towards metastatic protection. On the other hand, the contribution of adaptive immunity in response to primary tumors that may impact distant organ metastasis remains unclear, especially the long-range deployment of adaptive immune cells has rarely been studied. Overall design: To identify the components of immune microenvironment of pre-metastatic lungs, 20,000 CD45+ leukocytes were isolated by magnetic-activated cell sorting (MACS) from paired murine lung samples at day 28 post-inoculation.