CD39+PD-1+CD8+T cells mediate metastatic dormancy in breast cancer

Summary Some breast tumors metastasize aggressively whereas others remain in a state of metastatic dormancy for months or even years. The mechanism governing such metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identified a discrete population of CD39 + PD-1 + CD8 + T cells present both in primary tumors and in dormant metastasis, which was hardly found in aggressively metastasizing tumors. Using blocking antibodies, we found that dormancy depended on TNF α and IFN γ . Of note, immunotherapy reduced the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39 + PD-1 + CD8 + T cells prevented metastatic outgrowth. In human breast cancer, the frequency of CD39 + PD-1 + CD8 + but not of total CD8 + T cells correlated with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39 + PD-1 + CD8 + T cells for controlling experimental and human breast cancer. Furthermore, density of CD39 + PD-1 + CD8 + T cells may serve as a novel biomarker and may serve as a potential immunotherapy target. Thus, we discovered that a primary breast tumor primes a systemic, CD39 + PD-1 + CD8 + T cell response that is essential for metastatic dormancy in the lungs.