Immuno-oncology has seen a rapid growth in the past few years in terms of not only research, clinical development and investment but also expectations. It is quite clear, that although artificially boosting the body's immune system against cancer can do wonders, there is still a lot we need to understand.
There are several questions that remain to be answered before we can declare victory in the fight against cancer. To name just a few: What is the best way to trigger the immune response? Why immunotherapy works only for lucky few patients, even with the same type of cancer, and not for all?
One of the most exciting concepts in immuno-oncology looks at tumours as "hot" and "cold" and can shed some light on these questions. The distinction between "hot" and "cold" cancer is done based on the degree tumours are infiltrated with immune cells (high infiltration=hot, low infiltration=cold) and tumours genetic makeup - the more mutations the hotter the tumour.
Basically, hot tumours generally respond better to immuno-oncology drugs as they are packed with deviant proteins and the immune system has already dispatched lots of immune cells to the tumour; it is just the cancer manages to evade the immune cells.
Recently, BMS' two checkpoints inhibitors showed promising results in previously treated small cell lung cancer who had high number of gene mutations. This was an exploratory analysis but it clearly showed that the immune system, triggered by Opdivo with or without Yervoy, engaged more efficiently with tumours carrying high level of mutations (high tumour mutation burden, TMB).
This might be counter-intuitive, but at least in some cases, like lung cancer it appears, the 'hotter' the tumour the better the patient's chances. I think this is an important study as it makes the concept clinically relevant.
There is still a lot of work that needs to be done to fully exploit the biology behind this and to drive development of adequate therapeutic approaches. The recognition of the clinical relevance should lead many academic and pharma labs to look at ways to activate the immune system in patients with 'cold' tumours' and there is plenty of them out there.
“These exploratory TMB data from CheckMate -032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two I-O agents,” Dr. Matthew D. Hellmann, MD, study investigator at Memorial Sloan Kettering Cancer Center