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

Paulino Tallón de Lara, Héctor Castañón, Marijne Vermeer, Nicolás Núñez, Karina Silina, Bettina Sobottka, Joaquín Urdinez, Virginia Cecconi, Hideo Yagita, Farkhondeh Movahedian Attar, Stefanie Hiltbrunner, Isabelle Glarner, Holger Moch, Sònia Tugues, Burkhard Becher and Maries van den Broek ()
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Paulino Tallón de Lara: Institute of Experimental Immunology, University of Zurich
Héctor Castañón: Institute of Experimental Immunology, University of Zurich
Marijne Vermeer: Institute of Experimental Immunology, University of Zurich
Nicolás Núñez: Institute of Experimental Immunology, University of Zurich
Karina Silina: Institute of Experimental Immunology, University of Zurich
Bettina Sobottka: University Hospital Zurich
Joaquín Urdinez: Balgrist University Hospital, University of Zurich
Virginia Cecconi: Institute of Experimental Immunology, University of Zurich
Hideo Yagita: Juntendo University School of Medicine
Farkhondeh Movahedian Attar: Institute of Experimental Immunology, University of Zurich
Stefanie Hiltbrunner: Institute of Experimental Immunology, University of Zurich
Isabelle Glarner: Institute of Experimental Immunology, University of Zurich
Holger Moch: Comprehensive Cancer Center Zurich
Sònia Tugues: Institute of Experimental Immunology, University of Zurich
Burkhard Becher: Institute of Experimental Immunology, University of Zurich
Maries van den Broek: Institute of Experimental Immunology, University of Zurich

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21045-2

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