ASCO 2013

Role of microenvironment and stroma in cancer therapy

Dr Stephen Ansell - Mayo Clinic, Rochester, USA

Much of what we have done so far in researching cancer in general but lymphoma specifically has focussed on the cancer cell which in lymphoma is a B-cell, kind of a B-lymphocyte. But there’s increasing evidence, and this is what the focus of our discussion today was, on the microenvironment; those are other cells that are around the cancer cell that support its growth. That includes T-cells, some monocytes and macrophages as well as stromal cells. All of these are normal components of the lymph node but in this case rather than doing something good and suppressing the cancer, they’re actually providing assistance and help. And the cancer cells themselves are no help in that they then will suppress the microenvironment by getting regulatory elements, these are cells that usually damp down your immune system, bringing them into play and actually increasing the whole regulation of the environment.

What developments have we seen in this area?

There are a number of new treatments that are looking at doing one of two things: either removing these suppressive elements and these cells that are suppressing the microenvironment, or secondly activating immune cells. And there are a number of treatments, there’s an anti-PD1 antibody that has shown a lot of promise and data has been presented at this meeting. There is an anti-CTLA-4 antibody, known as ipilimumab, in combination with PD1 shown at this meeting with a lot of activity in melanoma and in other diseases. The same thing is true, also, in blood related cancers and so the microenvironment and the role of the immune system is becoming increasingly important.

Is the research for melanoma as exciting as they say it is?

I think that really is that exciting. I think that in times gone by melanoma was a disease with very few treatment options and that has dramatically changed with ipilimumab and now with the anti-PD1 antibody and the two used in combination. The results are very promising and I think, again, this is a new and exciting golden era, if you like, for treatment in melanoma. Treatment also is being expanded now into other diseases and similar results are being seen and that’s again very exciting.

What about ALK?

ALK as in the ALK positive cells that are present in tumour cells? Yes. So I think again there has been a lot of promise with directly inhibiting ALK and showing that that actually has a significant effect on the cancer cells. That’s true in certain solid tumours but also true now in certain kinds of lymphomas. So I think again a very specific therapy. That counterbalances the conversation about the microenvironment where ALK is very specific within the tumour cell and the microenvironment is obviously the cells around the tumour cell. So I think future therapies are going to be combinations of the two where we target the cancer cell and target the microenvironment all at the same time.

What should doctors in practice be making of this data?

I think again this is something that’s very rapidly going to translate into practice. Ipilimumab, the anti- CTLA-4 antibody is already commercially available and being used in melanoma. My prediction is that combinations with that and other checkpoint inhibitors are very soon going be available for patients and so I think this is a space that physicians should pay attention to because in combination with other standard approaches this may well be the future of treatment for these patients.

What about cancers other than melanoma?

Equally there have been very exciting results seen in other cancers – lung cancer with the anti-PD1 antibody. There are now trials on-going in Hodgkin lymphoma and non-Hodgkin lymphoma with the PD1 antibody with a lot of exciting results. So I think the future looks very bright for checkpoint inhibitors in general and immunological approaches as well.