Some breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+ T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+ T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not total CD8+ T cells correlates 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. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+ T cell response that favors metastatic dormancy in the lungs.

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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, 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. Of note, the 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. Here, 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.3