CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
By
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,
Maries van den Broek
Posted 03 Jun 2020
bioRxiv DOI: 10.1101/2020.06.02.126037
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. ### Competing Interest Statement The authors have declared no competing interest.
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