Cancer Stem Cells Connecting to Immunotherapy: Key Insights, Challenges, and Potential Treatment Opportunities

Abstract

Cancer continues to pose a significant challenge to global health, resulting in millions of deaths annually despite advancements in treatments like surgery, chemotherapy, and radiotherapy. A key factor complicating successful outcomes is the presence of cancer stem cells (CSCs), which possess distinctive features that facilitate tumor initiation and progression as well as resistance to therapies. These cells are adept at evading conventional treatments and can hinder the effectiveness of immunotherapy, often manipulating the tumor microenvironment to suppress immune responses. This review delves into the complex interplay between CSCs and immune cells, emphasizing their contributions to tumor heterogeneity and therapeutic resistance. By investigating the CSC niche in which these cells thrive and their complex interactions with the immune system, we aim to reveal new therapeutic avenues that could enhance patient outcomes and minimize the risk of recurrence. CSCs are characterized by remarkable self-renewal and plasticity, allowing them to transition between stem-like and differentiated states in response to various stimuli. Their existence within the CSC niche confers immune protection and maintains stem-like properties while promoting immune evasion. Activating key signaling pathways and specific surface markers is crucial in developing CSC traits, pointing to potential strategies for effective tumor eradication. Conventional therapies often fail to eliminate CSCs, which can lead to tumor recurrence. Therefore, innovative immunotherapeutic strategies such as dendritic cell vaccines (DC vaccines), chimeric antigen receptor (CAR) engineered T cells, and immune checkpoint inhibitors (ICIs) are under examination. This review sheds light on CSC's roles across different malignancies, highlighting the necessity for innovative targeted approaches in cancer treatment.

Keywords: CSC niche; cancer stem cells (CSCs); immune evasion; immunotherapy; tumor microenvironment (TME).

Figure 1

Characterizing cancer stem cells: fundamental hallmarks emerging attributes and related features.

Figure 2

Cancer stem cell properties in therapeutic resistance.

Figure 3

Intrinsic and extrinsic factors that influence the plasticity of CSCs.

Figure 4

Crosstalk between CSCs and immune cells in the TME.

Figure 5

Targeting cancer stem cells (CSCs) in combination with innovative strategies.