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CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
bioRxiv - Cancer Biology Pub Date : 2020-09-22 , DOI: 10.1101/2020.06.02.126037
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

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.

中文翻译:

CD39 + PD-1 + CD8 + T细胞介导乳腺癌的转移性休眠

一些乳腺肿瘤侵袭性转移,而另一些则处于转移性休眠状态长达数月甚至数年。控制这种转移性休眠的机制在很大程度上仍然未知。通过高参数单细胞作图,我们发现原发性肿瘤和休眠转移中均存在离散的CD39 + PD-1 + CD8 + T细胞群,而在积极转移性肿瘤中几乎没有发现。值得注意的是,纯化的CD39 + PD-1 + CD8 + T细胞的过继转移阻止了转移性生长。在人类乳腺癌中,CD39 + PD-1 + CD8 +的频率与全部CD8 + T细胞的频率与切除后的转移性复发复发(无疾病生存)相关,因此突显了CD39 + PD-1 + CD8 + T的生物学相关性用于控制实验性和人类乳腺癌的细胞。此外,CD39 + PD-1 + CD8 + T细胞的密度可以作为一种新型的生物标志物,并可以作为潜在的免疫治疗目标。在这里,我们发现原发性乳腺肿瘤引发了全身性CD39 + PD-1 + CD8 + T细胞反应,这对于肺部转移性休眠至关重要。
更新日期:2020-09-22
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