Targeting tumor-initiating cells to enhance cancer immunotherapy in digestive system tumors

Tumor-initiating cells (TICs), a distinct and critical subset of cancer cells, exhibit enhanced stemness and tumorigenic capabilities. These cells are characterized by their high plasticity, emerging from the conversion of non-TIC tumor cells. They play a pivotal role in promoting drug resistance and tumor relapse, major contributors to poor patient outcomes. TICs are adept at evading anti-tumor immune responses through the expression of immunosuppressive molecules and fostering an immunosuppressive tumor microenvironment. This ability not only enables them to modulate and escape the cytotoxic activities of immune cells but also diminishes the local anti-tumor immune pressure. The profound implications of TICs in cancer immunotherapy resistance underscore the necessity of in-depth studies in this field. This understanding is crucial for developing novel immunotherapeutic strategies that can specifically target and neutralize these cells. In addition to their immune evasion strategies, TICs also exhibit a remarkable capacity for phenotypic variation, contributing to tumor heterogeneity. This heterogeneity is closely linked to the challenges of treating cancer effectively, as it leads to varied responses to therapeutic interventions. 
The presence of TICs in digestive system tumors has been widely reported. Their association with drug resistance, tumor recurrence, and metastasis in these cancers has also been extensively studied. Recent research suggests that the presence of TICs may also be closely related to resistance to immunotherapy in these tumors.
 
In this context, this Research Topic aims to explore the latest advancements in understanding the complex role of TICs in the progression of digestive system tumors, particularly focusing on their contribution to immune evasion in digestive system tumors. Key areas of interest include, but are not limited to, the following:
(1) Mechanisms through which TICs contribute to immune evasion and tumor heterogeneity;
(2) Strategies to target TICs for enhancing the efficacy of cancer immunotherapy;
(3) The interplay between TICs, tumor microenvironment, and immune response;
(4) Novel methodologies for identifying and characterizing TICs in various cancer types;
(5) Clinical implications of TICs in cancer prognosis, therapy resistance, and relapse.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.