Erik Cressman (MD Anderson Cancer Center, Houston, USA) took to the podium, also at 2023 Global Embolization Oncology Symposium (GEST, 18–21 May, New York City, USA), to dive into why tumour ‘temperature’ matters—explaining what the terminology refers to, and its significance for patient treatment.
He first addressed how cancer is “eventual failure of the immune system”—depending on the source, Cressman explained that a single cell’s DNA can take “10,000 hits per day”. Of our roughly 100 trillion cells, five billion are replaced everyday, leading the presenter to posit that “on the one hand, it is amazing that we are not all sitting here with cancer, while on the other hand, it is amazing that the immune system works as well as it does”. Not all the cell damage that occurs leads to a tumour, but unfortunately, natural selection is at work in damaged or unregulated cells, and Cressman added how the selection process favours scenarios that evade or suppress immune surveillance.
Next, the speaker alluded to the “mixed bag” that is immunotherapy, which, while yielding “some inspiring success stories”, it also fails, which can be for a number of reasons. “It isa complicated thing,” he summarised, elaborating that some of the failures are “spectacular” in how they “unleash the immune system”. The older immunosuppressant drugs such as steroids are often not specific enough in responding to unregulated cell proliferation. Now, Cressman expanded, “we have these very highly specific antibodies that have a long-circulating half-life, [which you might only need]once every month or once every three months”. The downside of this type of immunotherapy is that “you are going to be hit with a high bill.
“The concept of an immunoscore to assess the tumours when we are talking about hot and cold” is well over a decade old, Cressman continued, coming to the pivotal focus of his presentation. The speaker referred to Galon and Bruni’s 2019 review to unpack this concept and “look at what is going on at the centre of the tumour and at the margin”. A low immunoscore correlates with a low response to T-cell checkpoint inhibition, Cressman stated, proceeding to celebrate that the prognostic value of immunoscore is “better than much of what we were taught”.
The presenter then showed delegates microscope images of hot versus cold tumours, where hot means a lot of immune cells throughout and cold, not being able to see any. He also showed the audience how “excluded” tumours are those that have a lot of immune cells, but which are yet to penetrate the tumour itself. “Suppressed” means there are some immune cells, “not particularly excluded”, but which do not function as typical immune cells.
“To summarise, the hot tumours have a high degree of T-cell and cytotoxic T-cell infiltration, and checkpoint activation is clearly going on”. Checkpoint inhibitors have a “greater likelihood of success” in these tumours, Cressman set out. Immunosuppressed tumour cells with an intermediate immunoscore have “poor, albeit not absent” T-cells and cytotoxic T-cell infiltration, and the presence of soluble inhibitory mediators, as well as T-cell checkpoints. There is a “modest response to immunotherapies” in these tumours. Immune-excluded tumours have “no T-cell infiltration inside the tumour bed and accumulation of T-cells at the tumour border”, as well as abnormal vasculature and hypoxia, and they yield a poor response when immunotherapies are used. “Cold” tumours have no T-cells either within or at the tumour edges, and there is failed T-cell priming, leading to poor response from immunotherapies.
“So, what can you do to improve outcomes? You can use image-guided injection of some of these antibodies to ramp up the immune system locally”, Cressman suggested, listing normalising the vascularity by triggering angiogenesis, addressing metabolism, restoring a normal pH as acidity is immunosuppressive, depleting immune-suppressive cell populations, and implementing a “combination of all of the above”, as additional strategies.