Immune evader cancer stem cells direct the perspective approaches to cancer immunotherapy

Abstract

Exploration of tumor immunity leads to the development of immune checkpoint inhibitors and cell-based immunotherapies which improve the clinical outcomes in several tumor types. However, the poor clinical efficacy of these treatments observed for other tumors could be attributed to the inherent complex tumor microenvironment (TME), cellular heterogeneity, and stemness driven by cancer stem cells (CSCs). CSC-specific characteristics provide the bulk tumor surveillance and resistance to entire eradication upon conventional therapies. CSCs-immune cells crosstalk creates an immunosuppressive TME that reshapes the stemness in tumor cells, resulting in tumor formation and progression. Thus, identifying the immunological features of CSCs could introduce the therapeutic targets with powerful antitumor responses. In this review, we summarized the role of immune cells providing CSCs to evade tumor immunity, and then discussed the intrinsic mechanisms represented by CSCs to promote tumors’ resistance to immunotherapies. Then, we outlined potent immunotherapeutic interventions followed by a perspective outlook on the use of nanomedicine-based drug delivery systems for controlled modulation of the immune system.

Characteristics of the cancer stem cell niche and therapeutic strategies

“…In the past few years, CSC-directed immunotherapy has emerged. Besides the antibodies targeting CSC-related signaling pathways mentioned above, novel anti-CSC immunotherapeutic approaches, such as cancer vaccines, checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T cell) therapies, have been developed [ 148 , 149 ]. One personalized neoantigen dendritic cell vaccine was chosen to treat metastatic lung cancer (NCT02956551).…”

Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy

“…Immune cells are an essential component of the stroma of the tumor and have a substantial impact on the outcome of this process. When both innate and adaptive immune cells are present in the TME, there is mounting evidence suggesting that these cells contribute to the progression of the tumor ( 48 – 50 ).…”

Recent Advances and Challenges in Cancer Immunotherapy

“…Due to their abundance in blood and their immediate reaction to inflammation and injury, their influence in the TME can set the tone for other immunosuppressive cells. DCs also infiltrate the TME but quickly adapt regulatory or tolerogenic phenotypes that promote tumor growth and immunoevasion [ 163 , 164 , 165 ]. Conventional DC types 1 (cDC1) and 2 (cDC2) play a key role as APCs and activate T cells for antitumor responses [ 166 , 167 , 168 ].…”