Cancer immunotherapy holds promise for colorectal cancer, but post-treatment relapse driven by cancer stem cells remains a challenge. Understanding CSC interactions and developing targeted therapies offer hope for transforming colorectal cancer treatment.
The following is a summary of “Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs,” published in the January 2024 issue of Hematology by Zhao et al.
Cancer immunotherapy has emerged as a promising paradigm in colorectal cancer treatment, with heightened attention to post-treatment relapse. Cancer stem cells (CSCs), a resilient subset with self-renewal capabilities, defy conventional therapies like radiotherapy and chemotherapy. Recent evidence underscores CSCs as pivotal drivers of tumor relapse post-immunotherapy.
Despite this recognition, the intricate interplay between CSCs and immune cells within the cancer niche remains largely unexplored. This comprehensive review delves into the characteristics of colorectal CSCs, their interactions with immune cells, and the prospects of CSC-centric immunotherapies. Colorectal CSCs exhibit distinctive features, including heightened expression of surface markers such as CD44, CD133, and Lgr5. Significantly, they manifest hyperactivation of stemness-related signaling pathways, including Wnt/β-catenin, Hippo/Yap1, Jak/Stat, and Notch, alongside intricate epigenetic modifications involving DNA methylation, histone modification, chromatin remodeling, and noncoding RNA action.
Moreover, colorectal CSCs showcase aberrant expression of immune-related genes, including MHC and immune checkpoint molecules, establishing reciprocal interactions with cancer niche cells across various tumorigenesis phases, encompassing initiation, maintenance, metastasis, and drug resistance. Various CSC-targeting therapies have undergone assessment, ranging from monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, tumor vaccines, and adoptive cell therapy to small molecule inhibitors.
The evolving landscape of CSC-/niche-targeting technologies, coupled with multidisciplinary insights, anticipates the emergence of novel therapies designed to eliminate CSCs and counteract their immunosuppressive microenvironment. The trajectory of such advancements holds promise for transforming the treatment paradigm of solid tumors, including colorectal cancer, heralding a future where therapeutic strategies adeptly navigate the intricacies of CSC-immune cell dynamics for enhanced clinical outcomes.
Source: ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00474-x
