How Checkpoint Inhibitors Can Activate the Immune System Against Lymphoma

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Topics include: Treatment and Understanding

In the recent past, lymphoma researchers have turned their attention to a phenomenon known as the “microenvironment.” Made up of three factors, the microenvironment involves healthy cells adjacent to the cancerous ones and helps keep the lymphoma alive in the face of treatment with chemotherapy. By releasing natural checks on the immune system, researchers believe that they may be able to employ it to kill the cancerous cells that would have survived. How does this therapy work, and where are we with this approach? In this video, hear from one of the leaders of the ASH MLB, Dr. Oliver Press, chief of the lymphoma research division at the Fred Hutchinson Cancer Research Center and the Co-Chair of the National Cancer Institute’s (NCI) Lymphoma Steering Committee. Dr. Press explains how activating the “infiltrating immune system” with checkpoint inhibitors may hold a valuable key for the treatment of lymphoma.

[Editor's Note: We will always be grateful for Dr. Press’ dedication to research, excellent care and devotion to patients, including often taking time to be part of Patient Power programs.]

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello and welcome to Patient Power. I’m Andrew Schorr. This program is sponsored by the Seattle Cancer Care Alliance.

There continues to be growing understanding of the science behind cancer and specifically lymphoma. Joining us now to help us understand that is a leader in the field: that’s Dr. Oliver Press who is the director of the clinical research division at the Fred Hutchinson Cancer Research Center in Seattle and sees lymphoma patients at the Seattle Cancer Care Alliance.

Dr. Press, welcome back to Patient Power.

Dr. Press:

Thank you for inviting me.

Andrew Schorr:

Dr. Press, help us understand what we know now about the relationship between healthy cells supporting lymphoma, cancerous cells.

Dr. Press:

Lymphoma specialists used to believe that whether a lymphoma responded to a new treatment and whether a patient was cured [were] almost entirely dependent on features of the lymphoma cells, that is what kinds of mutations they had and their growth rate, etcetera. However, we now realize that the microenvironment, that is the surrounding normal cells, are just as important in how a lymphoma responds to treatments and whether a patient survives or doesn’t.

There are several components of this microenvironment, at least three really important ones:

First is a supporting scaffold of normal cells called cancer associated fibroblasts that support and nurture and give nutrients to the cancer cells.

Second are the tumor blood cells that infiltrate the lymphoma.

Third is an infiltrating immune system that has several components.

Andrew Schorr:

As you gain that understanding of the biology, if you will, where are we now with treatment to break that connection between the healthy cells and the cancer cells?

Dr. Press:

Emerging knowledge is particularly pertinent regarding the infiltrating immune cells. There are both good immune cells and bad immune cells. The body does try to fight off cancers with the immune system and to do that, it uses both the adaptive immune system, such as killer T lymphocytes, and the innate immune system, which includes natural killer cells and macrophages, to try to destroy the lymphoma. But the body also has a check on the immune system with T-regulatory cells and other cells that control the magnitude of the immune response, to try to prevent adverse effects from the immune system. There’s a balance between turning on the immune system and turning off the immune system. New investigations are trying to control this balance so that we can activate the immune system when we want it to kill the lymphoma and then shut it down when the tumor is cured so that autoimmune disease does not develop.

Andrew Schorr:

Dr. Press, you’re a leader in clinical research, of course. Tell patients where we are now with manipulating the immune system to turn on in the right way or turn off in the right way, to help them.

Dr. Press:

Some of the most exciting developments recently have been in the recognition of checkpoints for the immune system. There are certain molecules that turn on and off the immune cells, and now there are monoclonal antibodies that can manipulate those checkpoints, the so-called checkpoint inhibitors. There are antibodies against molecules called PD1 and PDL1 and CD134 and CD137, but the idea is that it helps modulate the immune system.

A good way to think about it is that the immune system has both a gas pedal and a brake. At any one point in time, when a lymphoma is present, usually both the gas pedal and the brake are on at the same time. When we use these checkpoint inhibitors, we’re releasing the pressure on the brake and letting the immune system race forward and then, if we need to, we can put our foot back on the brake and take it off the accelerator. We’re just beginning to learn how to manipulate this balance, and preliminary studies have been very encouraging.

Andrew Schorr:

Dr. Press, you’ve been at this a long time. How excited are you for patients on what this could mean even in the near term or long term?

Dr. Press:

I think this is, by far and a way, the most exciting time for lymphoma research. We have so much knowledge now about the genomics and the epigenomics of lymphoma. We have so many tools and so many exciting avenues. I think the combination of these checkpoint inhibitors as well as new molecules that use signaling inhibitors like ibrutinib (Imbruvica) and idelalisib (Zydelig) and ABT-199, particularly when used in combination, I think, heralds a really exciting future for lymphoma therapy and lymphoma patients.

Andrew Schorr:

Dr. Oliver Press, director of the clinical research division at Fred Hutchinson Cancer Research Center and from the Seattle Cancer Care Alliance, thank you for your dedication to patients and for being with us once again.

Dr. Press:

Thank you.

Andrew Schorr:

Certainly good news for patients as we gain an understanding of the immune system in fighting their cancer.

I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on December 5, 2017