The incidence and mortality rates of gastrointestinal tumors account for 26%and 35%of global malignant tumors,respectively,and continue to rise annually.Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors,as well as establishing precise molecularly targeted intervention strategies,have become critical scientific challenges in oncology research.Doublecortin-like kinase 1(DCLK1),a type II transmembrane protein harboring serine/threonine kinase domains,is well-recognized as a specific molecular marker for cancer stem cells.DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells,while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment.In recent years,tissue-resident memory T cells(TRM),characterized by their sustained tissue residency and potent antitumor immune efficacy,have emerged as a novel avenue for cancer immunotherapy.This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors,with a focus on its potential association with TRM cell functional activation,aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.

The incidence and mortality rates of gastrointestinal tumors account for 26%and 35%of global malignant tumors,respectively,and continue to rise annually.Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors,as well as establishing precise molecularly targeted intervention strategies,have become critical scientific challenges in oncology research.Doublecortin-like kinase 1(DCLK1),a type II transmembrane protein harboring serine/threonine kinase domains,is well-recognized as a specific molecular marker for cancer stem cells.DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells,while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment.In recent years,tissue-resident memory T cells(TRM),characterized by their sustained tissue residency and potent antitumor immune efficacy,have emerged as a novel avenue for cancer immunotherapy.This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors,with a focus on its potential association with TRM cell functional activation,aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.