Abstract:The concept of the stem cell niche (microenvironment) has been proposed many decades ago, and the pivotal role of niche in controlling stem cells’ property has been documented in several well characterized stem cell systems: hematopoietic, skin, and intestine. Despite these advancements, the debate over which cellular components in bone marrow are key to hematopoietic stem cells (HSCs) has been ongoing. Here our new discoveries unrevealed a ‘zone’ concept that beyond the single-cell niche dogma defined initially in Flies and C. elegans. 

Accumulated evidence supports the concept that tumor-initiating stem cells (TSCs or CSCs) lie at the root of tumor/cancer and are largely responsible for the commonly observed resistance to chemoradiotherapy (CRT) and frequent relapse of disease. How does a subset of TSCs, or therapy refractory TSC (TrTSC), survive and support tumor regrowth post treatment is a fundamental biological question and clinically unsolved problem? Recently, we reported that CSCs can intrinsically escape immune attacking and at the same time can also shape the TME into an immunosuppressive barrier. Molecularly, β-catenin appears to regulate expressions of a broad range of immune checkpoints, thus empowering the immune escape capabilities of CSCs. In summary, overcoming both the extrinsic immunosuppressive barrier and intrinsic immune escape has the potential to increase the efficacy of checkpoint inhibition therapies against various cancers in the future.