Are Cancer Stem Cells a Suitable Target for Breast Cancer Immunotherapy?

Abstract

There is substantial evidence to suggest that complete tumor eradication relies on the effective elimination of cancer stem cells (CSCs). CSCs have been widely described as mediators of resistance to conventional therapies, including chemo- and radiotherapy, as well as of tumor metastasization and relapse in different tumor types, including breast cancer. However, the resistant phenotype of CSCs makes their targeting a tough task, and immunotherapy may therefore be an interesting option. Nevertheless, although immunotherapeutic approaches to cancer treatment have generated great enthusiasm due to recent success in clinics, breast cancer treatment mostly relies on standard approaches. In this context, we review the existing literature on the immunological properties of breast CSC and immunotherapeutic approaches to them. We will thus attempt to clarify whether there is room for the immunotargeting of breast CSCs in the current landscape of breast cancer therapies. Finally, we will provide our opinion on the CSC-targeting immunotherapeutic strategies that could prospectively be attempted.

Targeting cancer stem cell plasticity in triple-negative breast cancer

“…Immune checkpoint inhibitors alone show no efficiency in stem cell-like TNBC, but they can activate the immune system to restrain CSCs in combination with messenger RNA (mRNA) ligand-dependent corepressor (LCOR) therapy [ 124 ]. Besides mAbs, vaccines, and small molecules such as ruxolitinib or repair have also been used to target the CSC/immune-microenvironment interaction in clinical trials [ 125 ].…”

“…Immunebased therapies such as CAR-T cells targeting CSCs in TNBC are also being developed, and trophoblast cell surface antigen 2 (TROP2), disialoganglioside GD2 (GD2), receptor tyrosine kinase-like orphan receptor 1 (ROR1), mucin 1 (MUC1), and EpCAM promise targets [123]. Immune checkpoint inhibitors alone show no efficiency in stem cell-like TNBC, but they can activate the immune system to restrain CSCs in combination with messenger RNA (mRNA) ligand-dependent corepressor (LCOR) therapy [124]. Besides mAbs, vaccines, and small molecules such as ruxolitinib or repair have also been used to target the CSC/immunemicroenvironment interaction in clinical trials [125].…”

Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches

“…Vaccines against BCSC are also being studied—vaccines containing human BCSC-lysates have been shown to prolong the lives of mice with BC. Other types of vaccines have also been found to target BCSC and reduce tumor growth (reviewed in [ 467 ]).…”