From the Director

Changing the Environment of Cancer from the Inside and the Outside

Author: George Weiner
Date: 2017-12-15 09:22:00

Last month, I attended back-to-back meetings in Washington D.C. Both had a cancer focus, but otherwise it appeared there was little in common. The first was a meeting of the Society for the Immunotherapy of Cancer where the latest scientific and clinical advances in cancer immunotherapy were discussed. The second was a meeting of the National Cancer Policy Forum that included a workshop where we discussed approaches to helping cancer patients navigate the complexities of the health care system.

At the cancer immunotherapy meeting, there was a high level of excitement about the rapid advances taking place in using the immune system to treat cancer. Not only are we figuring out how the immune system responds to cancer, we are now able to use this knowledge to modify the immune system and successfully treat cancer in an increasing number of patients. At the core of this progress is our improved understanding of the tumor “microenvironment.” Cancer cells don’t exist in a vacuum. In many tumors, cancer cells are surrounded by non-cancerous cells, including cells of the immune system which make up the tumor microenvironment. Over the past decade we have identified a group of molecules on the surface of cancer cells that help them to hide from neighboring immune system cells. This explains why some cancers grow despite the presence of immune system cells in the tumor microenvironment. A way to think about this is to think of these molecules as a cancer cell’s equivalent of Harry Potter’s “invisibility cloak.” It makes the cancer cells invisible to the immune cells that are present in the same tumor microenvironment.   With this knowledge, we have created a new type of cancer therapy known as checkpoint blockade to remove the cancer cell’s “invisibility cloak.” This allows the immune system cells in the microenvironment to recognize and reject the cancer.

We are also learning that modifying the tumor microenvironment does not work in every case. In some cancers, the immune system cells in the microenvironment are not able to recognize and eliminate the cancer cells even with checkpoint blockade treatment. One approach to addressing this challenge is to add cancer-fighting immune system cells that are not naturally found in the tumor microenvironment. These cells, known as CAR-T cells, are produced in the laboratory by modifying the patient’s own immune system cells so they can effectively attack the cancer. The CAR-T cells are given back to the patient and travel via the blood stream into the tumor microenvironment where they can kill the cancer. This approach has been particularly exciting and effective in select leukemias and lymphomas, and is now being tried in other cancer types as well.

In other words, cancer immunotherapy can sometimes succeed by empowering immune system cells that are already inside the tumor microenvironment (e.g. checkpoint blockade) while other times we need to start with something new from outside the tumor micro-environment (e.g. CAR-T cells).

OK, enough about what happens at the micro level – let’s get macro and consider the real world where real patients live. The environment is vital there as well. At the meeting on patient navigation, we discussed the many obstacles patients face in the environment of the health system and their own communities when they are in need of cancer care. These include ineffective patient coordination within health care systems, differences in culture that impact on communication between the patient and caregivers, transportation issues, financial issues and other complex social factors. The result is that, way too often, patients get lost in the system and do not receive the care they need and deserve. One approach is to modify the environment within the health care system to make it more patient friendly and responsive to the diversity of the patients we serve. A complementary approach is to start outside the health care system and use patient navigators. Patient navigators are individuals who often come from the same community as the patient and are also familiar with the health care environment. Patient navigators help guide patients through the system in a broad variety of ways such as arranging for appointments, transportation, helping sort through financial issues, explaining a diagnosis or treatment plan in language the patient can understand or simply being a good listener.

In other words, enhancing access to care can sometimes succeed by modifying the operations within the health care system while other times we need to start with something new from outside the system such as patient navigators. So… at the micro level when considering cancer immunotherapy and the tumor microenvironment, and at the macro level when considering access to care and the health care environment, sometimes we can succeed by modifying the environment that already exists. Other times, such modification is not adequate and we need bring novel resources into the environment to achieve our goal. In addition to the goal of reducing the burden of cancer, it seems my cancer immunotherapy meeting and patient navigation meeting had something else in common after all.

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