Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named “common factor” in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.
Bibliographical noteFunding Information:
This work was supported by funding from the National Research Foundation of Korea (NRF-2019R1A6A3A01096338 to S.J. Oh and NRF-2017R1A2A1A17069818, NRF-2019R1A4A1029000, and NRF-2019M3A9A8066884 to T.W. Kim).
© The Korean Association of Immunologists 2020.
- Common factor
- Multi-malignant phenotypes
- Therapy-refractory cancer
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases