Abstract 2646: CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

Abstract

Abstract Although metastatic disease can be present already at diagnosis, in some patients it appears months or years after resection of the primary tumor. This is thought to be due to the ability of some tumor cells to remain dormant after metastatic seeding. It is not known how dormancy is controlled, but there is evidence for tumor cell-intrinsic and -extrinsic mechanisms including immune defense. Here we found in preclinical models of breast cancer that metastatic dormancy was fully controlled by T cells. 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 spontaneous dormant metastasis, whereas this population is hardly found in aggressively metastasizing tumors. Surprisingly, despite expressing many exhaustion markers, this population was rich in effector molecules and cytokines that induced dormancy in tumor cells. Of note, the adoptive transfer of purified CD39+PD-1+CD8+ T cells prevented metastatic outgrowth. Thus, we discovered that primary breast tumors prime CD39+PD-1+CD8+ T cells that induce metastatic dormancy in distal disseminated tumor cells in the lungs. Citation Format: Paulino Tallón de Lara, Héctor Castañón Cuadrado, Marijne Vermeer, Nicolás Núñez, Joaquín Urdínez, Virginia Cecconi, Farkhondeh Movahedian Attar, Isabelle Glarner, Stefanie Hiltbrunner, Sonia Tugues, Burkhard Becher, Maries van den Broek. CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2646.