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CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer. 2021
Paulino Tallón de Lara, and
Héctor Castañón, and
Marijne Vermeer, and
Nicolás Núñez, and
Karina Silina, and
Bettina Sobottka, and
Joaquín Urdinez, and
Virginia Cecconi, and
Hideo Yagita, and
Farkhondeh Movahedian Attar, and
Stefanie Hiltbrunner, and
Isabelle Glarner, and
Holger Moch, and
Sònia Tugues, and
Burkhard Becher, and
Maries van den Broek
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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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