Abstract PR07: Quiescent cancer cells form immunotherapy resistant reservoirs by forming an immune suppressive niche

Abstract

Abstract Immunotherapy is a promising treatment for Triple-Negative Breast Cancer (TNBC), but patients recur, arising the need to understand mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that survive T-cell attack while still expressing the targeted antigen are in a quiescent state. Quiescent Cancer Cells (QCCs) are found clustering together forming intra-tumor cold regions with reduced immune infiltration. QCCs display superior tumorigenic capacity and higher expression of stemness genes than their proliferative counterparts. We adapted single-cell-RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside the QCC niches. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T-cells, tumor-protective fibroblasts, and suppressive dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their specific intra-tumor location and their proximity to functionally disntinct sub-populations of tumor cells. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that alters fibroblasts and dendritic cells leading to T cell dysfunction. Eliminating QCCs holds the promise to counteract resistance to immunotherapy and prevent disease recurrence in TNBC. This abstract is also being presented as Poster P007. Citation Format: Judith Agudo. Quiescent cancer cells form immunotherapy resistant reservoirs by forming an immune suppressive niche [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr PR07.