Title:Is there a Role for Epigenetic Enhancement of Immunomodulatory Approaches to Cancer Treatment?
Volume: 18
Issue: 1
Author(s): Kirsty J. Flower, Sadaf Ghaem-Maghami and Robert Brown*
Affiliation:
- Department of Surgery and Cancer, Imperial College London, London,United Kingdom
Keywords:
Cancer immunotherapy, immune-evasive tumour cells, immunomodulatory agents, tumour microenvironment, radiotherapy,
chemotherapy.
Abstract: The efficacy of cancer immunotherapy relies on the ability of the host immune system to
recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile
area of medical research, with positive clinical trials showing durable responses, attention must be
paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting
by the host could itself select for immune-evasive tumour cells during tumour development
leading to immunotherapy resistance. One such mechanism of non-efficacy or resistance is
the epigenetic silencing of a specific gene required in the immunotherapy response pathway. Epigenetics
is the study of the control of expression patterns in a cell via mechanisms not involving a
change in DNA sequence. All tumour types show aberrant epigenetic regulation of genes involved
in all the hallmarks of cancer, including immunomodulation. Inhibition of key enzymes involved in
maintenance of epigenetic states is another important area of research for new treatment strategies
for cancer. Could epigenetic therapies be used to successfully enhance the action of immunomodulatory
agents in cancer, and are they acting in the way we imagine? An understanding of the effects of
epigenetic therapies on immunological pathways in both the tumour and host cells, especially the
tumour microenvironment, will be essential to further develop such combination approaches.
