Chen & Mellman’s cancer-immunity cycle breaks down how the immune system mounts an attack against cancer into seven simple steps.
Depending on what step in the cycle is impacted – the early, middle or late steps - it’s possible to group cancer-immune phenotypes into three broad categories: immune-desert tumours, immune-excluded tumours, and inflamed tumours.
To bring these phenotypes to life, Genentech likens them to going on a mission to the moon:
1. Immune-desert tumours: Failure to Launch
If the rocket can’t get off the ground, the mission has failed. And this is the same if the immune system can’t launch an effective attack against cancer cells. Potential reasons for this include a lack of foreign antigens on cancer cells or problems with immune system signalling and activation.
2. Immune-excluded tumours: Lost in Space
Just as if the rocket never actually reaches the moon - if immune cells can’t enter a tumour, they won’t succeed in killing cancer cells. This can happen if their entry is impeded by physical barriers, such as blood vessel walls or connective tissue.
3. Inflamed tumour: Mission not quite accomplished
Even if there is a successful moon landing, the astronaut – or the immune system – may still not complete their mission. An example of this might be that molecular signals shut down the immune cell’s activity.
The enormous inter-patient variability seen in response to immunotherapies led Chen & Mellman to go even further, proposing their cancer-immune setpoint theory. This reflects that an individual’s cancer-immune phenotype come about through a complex interplay of many different factors – the microbiome, genetics and the environment. And together, these determine their likelihood of an effective immune response to their cancer.
But the framework isn’t the final version - it will continue to rapidly evolve as an avalanche of new discoveries continue are made in this exciting field of research.
We want to accelerate this evolution through crowdsourcing. But this requires your help. Please go to the interactive framework to add or comment on factors.
This post is based on a longer article ‘Beyond the Cycle’ – which you can read in full on the Roche website.