Cellular and molecular mechanisms in cancer immune escape: a comprehensive review

Abstract

Immune escape is the final phase of cancer immunoediting process wherein cancer modulates our immune system to escape from being destroyed by it. Many cellular and molecular events govern the cancer’s evasion of host immune response. The tumor undergoes continuous remodeling at the genetic, epigenetic and metabolic level to acquire resistance to apoptosis. At the same time, it effectively modifies all the components of the host’s immunome so as to escape from its antitumor effects. Moreover, it induces accumulation of suppressive cells like Treg and myeloid derived suppressor cells and factors which also enable it to elude the immune system. Recent research in this area helps in defining the role of newer players like miRNAs and exosomes in immune escape. The immunotherapeutic approaches developed to target the escape phase appear quite promising; however, the quest for a perfect therapeutic agent that can achieve maximum cure with minimal toxicity continues.

Keywords::

• cancer
• immune escape
• myeloid-derived suppressor cells
• protumor
• T regulatory cells

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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

Key issues

• Cancer immune escape is the most extensively studied phase of cancer immunoediting process.

• All the components of host’s immune arm are modulated by the cancer so as to escape the immune response.

• Besides immune cells and secreted factors the tumor cell metabolism and various signaling pathways also play an important part in cancer’s evasion of immune system.

• Besides genetic factors, the epigenetics and regulatory miRNAs are emerging as important players in immune escape.

• Suppressor cells like Tregs and myeloid-derived suppressor cells promote cancer and are proving to be the frontline targets of upcoming immunotherapeutics.

• The cellular and molecular components prevalent in the tumor microenvironment at a particular point of time ultimately decide the result of ongoing battle between the cancer and our immune process.

• The list of agents targeting immune escape is expanding and future of cancer immunotherapy appears promising.

Notes