Five Questions With an Immunotherapy Expert

CURE spoke with Jason Luke, M.D., about some of the pressing topics in the field of immunotherapy.
Immunotherapy is showing great promise in many cancer tumor types as medical experts continue to expand their studies in the field.

In an interview with CURE, Jason Luke, M.D., assistant professor of medicine, University of Chicago, discussed the biology of immunotherapy, similarities across tumor types, the importance of biomarkers and what still needs to happen in the future.

What are some of the common questions in this field?

In the field of immunotherapeutics, the difference between cancers isn’t really the relevant point – we don’t think. It’s more the difference between the immune system response to cancer. So we have to sort of take a step back and rethink the way we thought about cancer therapeutics in the past.

Shared features across different tumor types can include the things like mutations, which we had commonly thought about, but we tend to think of them in a different way than we did in the past. So instead of being focused specifically on mutations like RAS or BRAF – it’s more the number of mutations than the consequent downstream number of neoantigens generated that different tumor types may or may not have. Then the quality of the baseline immune response in the patient can really dictate how well these drugs can then work.

That can be measured a number of different ways – PD-L1 assay, gene expression profiling and detecting the diversity of the T-cell receptor. There are a number of technologies that are evolving that are going to help us understand how to apply immunotherapy more broadly, not so much in a cancer-specific way in terms of disease histologies, but rather in an individual cancer sort of way aiming at the quality of the immune response that they already have at baseline. 

Do you think one day, perhaps, we will have immunotherapy to treat almost all tumor types?

Yes. That’s our overriding hope, and I think the future probably won’t be immunotherapy alone for many patients. There seem to be sort of three main phenotypes in patients – one is with a very robust response and they respond well to PD-1 antibodies, those patients who sort of have an intermediate response where you can get some activity and then some patients are like no immune response.

Those patients with immunotherapy on its own probably aren’t going to have much activity. But almost certainly, even in those patients, combining immunotherapy with chemotherapy or targeted therapies or other therapies will enhance the benefit and hopefully generate long-term, potentially cures in some patients.

We see immunotherapy, particularly right now in melanoma and lung cancer, and it’s working really well, but then we look at some other tumor types and there is difficulty. What makes immunotherapy work so well in some situations? Where do we need to go to get it to work in others?

Well, the paradigm really is thinking about what the baseline immune response of the patient is and in some tumors we see, in most patients, a very robust anti-tumor immune response. You mention melanoma and lung cancer, and there are hypotheses out there that part of the reason that those baseline immune responses are so robust is a number of neoantigens or mutations that are different between the cancer and the regular tissue are enough that the immune system will notice that.

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