Decitabine: a promising epi-immunotherapeutic agent in solid tumors

Abstract

The incidence of malignancies is increasing worldwide. Despite early detection, surgical resection, chemotherapy and radiotherapy, numerous patients continue to die from metastasis or recurrence. The immune system has the capacity to eradicate cancer cells; however, many tumors, especially solid tumors, present considerable challenges that render immune cells ineffectual, making cancer cells almost ‘invisible’ to the immune system. Compelling evidence has demonstrated that DNA methylation is involved in tumor development and progression, leading to the impaired immunogenicity and immune recognition of cancer cells. The hypomethylating agent decitabine has been shown to have therapeutic effects in malignancies and exhibits an effective immune efficacy in eliminating cancer cells. Based on the hypomethylating and immune remodeling effects of decitabine, we propose in this review that decitabine can be considered an epi-immunotherapeutic agent. We summarize the results of recent preclinical studies and clinical trials for decitabine and discuss the connections among its hypomethylating effect, immune-activated mechanisms and clinical activity in solid tumors, keeping in mind the goal of optimizing dosing schedules.

Keywords:

• co-stimulatory molecules
• cancer testis antigen
• decitabine
• HLA class I
• immune response
• immunotherapy
• methylation

Financial & competing interests disclosure

The research related to this work in the authors’ laboratory was supported by the grants from the National Natural Science Foundation of China (NO. 81101486, 81272867, 31270820, 81230061 and 81472838) and is partially supported by National Basic Science and Development Programme of China (2012CB518103). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Decitabine is a novel epigenetic agent and has anti-tumor activity in solid tumors.

• Aberrant methylation of immune-related genes promoters leads to immune escape of cancer cells.

• Decitabine re-activates specific immune response through inducing the demethylation of cancer testis antigens, human leukocyte antigen class I and co-stimulatory molecules.

• Decitabine can be used in combination with other therapeutic strategies, such as radiochemotherapy, immunotherapy or other epigenetic agents.

Notes