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Review
. 2021 May 20;13(10):2491.
doi: 10.3390/cancers13102491.

Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy

Hiroko Ishii  1 , Said M Afify  2   3 , Ghmkin Hassan  2 , David S Salomon  4 , Masaharu Seno  2
Affiliations
Review

Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy

Hiroko Ishii et al. Cancers (Basel). .

Abstract

The immune system has been found to be suppressed in cancer patients. Cancer cells are extremely resistant to chemotherapeutic drugs, conventional immunotherapy, or cancer antigen vaccine therapy. Cancer immunotherapy, which is mainly based on immune checkpoint inhibitors, such as those for PD-1, PD-L1, and CTLA4, is an effective treatment method. However, no immunotherapeutic target has been found that retains validity in the face of tumor diversity. The transforming growth factor (TGF)-β cytokine family possesses broad biological activity and is involved in the induction and/or transdifferentiation of helper T cells, which are important in immunotherapy. Nodal is a member of the TGF-β family playing important roles in tissue stem cells and cancer stem cells (CSCs), interacting with the co-receptor Cripto-1, as well as with Activin type IB (Alk4) and Activin typeIIreceptors, and maintaining stemness and Notch and Wnt/β-catenin signaling in CSCs. In recent years, it has been reported that Cripto-1 could be a potential therapeutic target in CSCs. Here, we review the accumulated literature on the molecular mechanisms by which Cripto-1 functions in CSCs and discuss the potential of Cripto-1 as an immunotherapeutic target in CSCs.

Keywords: Cripto-1; TGF-β; antibody; cancer stem cells; immunotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Strategies for targeting cancer cells with monoclonal antibodies (Mab). Mabs can be conjugated with toxins or nanoparticles that deliver drugs and toxic materials to cancer cells. Mabs could also target cancer cell receptors and inhibit cell signaling pathways responsible for cell growth, stem cell maintenance, and metastasis. Antibodies could bind ligands or receptors to prevent their interaction. Finally, antibodies could recruit different immune cells and activate host immunity against cancer cells.
Figure 2
Figure 2
Signaling pathways that are activated by Cripto-1. Left: Cripto-1 Nodal-independent signaling via Glypican-1 activating c-Src/MAPK/AKT downstream signaling. Right: Canonical Nodal/ALK4,7/Smad2 signaling with Cripto-1 and Grp78 as co-receptor.
Figure 3
Figure 3
Antagonizing Cripto-1 can decrease metastasis and tumor recurrence. A summary of the tumor-suppressing effect of Cripto-1 antagonists on metastasis and recurrence of tumors.
See this image and copyright information in PMC

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