Immunotherapy may increase tumour growth in some cases

Scientists at Imperial College London have found that cancer immunotherapy, intended to boost the body’s immune system in order to fight tumours, may actually be having the opposite effect in some cancers. The researchers believe this could have implications for the effectiveness of immunotherapy in combating human cancers caused by inflammation, such as some liver and colon cancers.

Published in the journal Nature Communications, the study analysed a part of the immune system called NKG2D (Natural Killer Group 2 member D). NKG2D is a type of immunoreceptor — a molecule present on the surface of the body’s immune cells that recognises signals from normal cells that are distressed. For example, if a normal cell is infected with a virus, it will display molecules on its surface that the NKG2D immunoreceptor can detect. The immune cell then directs a lethal hit that destroys the infected cell.

Dr Nadia Guerra, lead author of the study, first showed 10 years ago that this mechanism also works against cancerous tumours — demonstrated by the fact that tumours grew faster in mice that had their NKG2D activity suppressed. Since then, she said, “Immunotherapies have shown unprecedented successes in treating cancer patients with advanced forms of cancer, especially metastatic melanomas.”

However, NKG2D also contributes to inflammation and has been found to play a role in chronic inflammatory disorders, such as Crohn’s disease. In this case, the NKG2D misfires and attacks normal cells instead of damaged ones.

Dr Guerra and her team recently looked into whether NKG2D’s roles in chronic inflammation and cancer could help tumours to grow. To do this, they used a mouse model of liver cancer driven by inflammation. They found that the tumours actually grew faster in mice with functional NKG2D than in mice that lacked NKG2D.

“NKG2D is a potent anti-tumour agent, but we have found that it might actually have the opposite effect in tumours that arise and/or grow from a background of chronic inflammation,” Dr Guerra said. This is because in these environments, the liver tissue undergoes cycles of damage and repair continuously as it is fought by NKG2D, making the cells more at risk of developing genetic mutations.

“The paradoxical effect of NKG2D we discovered exposes the need to selectively target the types of cancer that will benefit from NKG2D-based immunotherapy,” Dr Guerra said. “What is beneficial in fighting one type of cancer might have the opposite effect in another.

“We need to be more precise when administering a chosen therapy to a particular type of cancer. Our data unravels a conceptual shift that will inform which cancer these new therapies can benefit the most, and help match the best therapy to each patient.”

This piece is a modified version of a news item published by Imperial College London under CC BY-NC-SA 4.0, and is published here under the same licence.