Characterization of Immune Evasion Mechanisms of Breast Cancer Disseminated Cells in the Lung

Abstract

Despite recent advances in cancer immunotherapies, many patients still die from metastasis. Metastases arise from cells that escape the primary tumor and disseminate to distant organs. A more comprehensive understanding of how disseminated tumor cells (DTCs) survive is therefore needed to develop therapeutic strategies against them. In this work, we took advantage of a well- established model of breast cancer lung metastasis to characterize the immune evasion of DTCs in the lung. We found that the presence of a mammary tumor led to reduced numbers of DTCs in lungs upon tail vein injection of breast cancer cells compared to tail vein injection alone. This was dependent on the presence of CD8+ T cells, suggesting that anti-tumor T cells were present in circulation and could eliminate DTCs in the lung. By engineering breast cancer cells to express green fluorescent protein (GFP), we were able to detect an expansion of GFP-specific CD8+ T cells in lungs 14 days post tail vein injection. Thus, all these data indicated that systemic and local immunity in lungs can target DTCs and yet some of them still survive and give rise to lung metastases. In order to uncover how DTCs evade adaptive immune responses, we are setting up a platform to characterize the metastatic niches around DTCs in our breast cancer metastasis model. Myeloid-derived suppressive cells (MDSCs) and regulatory T cells (Tregs) were enriched in the lungs of primary tumor-primed mice, which might explain how DTCs survived despite high infiltration of CD8+ T cells. How other immune cells help DTCs to escape CD8+ T cell killing needs further investigations.