Abstract 1491: Immune resistance emerges from tumor-initiating stem cells

The remarkable capacity of the long-lived stem cells-like population to self-renew, initiate and propagate a tumor placed these cancer stem cells (CSC) at the root of tumorigenesis. Many unique molecular features of stem cells endow these key population with specialized properties to drive tumor formation. However, in order to achieve these functions, the neoplastic stem cells must first overcome the immune barrier. Although it has long been postulated that, as the core of a tumor, CSCs must be superior at evading the immune detection, direct evidence is still lacking to demonstrate this stem cell trait. Another important feature of CSCs is that these cells are programed to resist traditional cancer treatments, including chemotherapy and radiation. Yet, it is still unexplored how CSCs react to the immunotherapy, which just start to revolutionize the cancer treatments. In order to address these fascinating questions, we have designed a spontaneous skin squamous cell carcinoma (SCC) mouse model that can be effectively targeted by adoptive cell transfer (ACT)-based immunotherapy, without losing the targeted tumor antigen. Employing this model, we have lineage traced the fate of tumor-initiating stem cells during and after ACT treatment. In this study, we will present data demonstrating that a subset of TGFβ-responding CSCs, residing at the tumor-stromal interface, are always able to survive from the injected CD8+ T cell treatment and give rise to the relapsed tumor. Furthermore, the extensive profiling of ACT surviving stem cells revealed that multiple immune resistant pathways are highly up-regulated in these stem cells. In addition, TGFβ appears to orchestrate these immune resistant processes in the tumor-initiating stem cells. This study highlights CSCs as the core to mediate immune evasion. Citation Format: Yuxuan Miao. Immune resistance emerges from tumor-initiating stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1491.