Unblocking the Potential of Immunotherapy

Dr. Sterman

“I spent 20 years trying to do immunotherapy and we weren’t as successful as we wanted to be probably because we didn’t recognize the degree to which the environment within the tumor is so suppressive,” said Dr. Dan Sterman during our latest Meet the Mesothelioma Experts broadcast referring to the inability of the immune system to attack certain tumors.

Dr. Sterman, a professor of pulmonary and critical care medicine at the NYU School of Medicine, is also director of the division of pulmonary, critical care, and sleep medicine and director of the multidisciplinary pulmonary oncology program at NYU’s Langone Medical Center in New York City.

In our newest Meet the Mesothelioma Experts session, Dr. Sterman discussed immunotherapy, its implications, and the importance of qualifying candidates to enroll in clinical trials. With over 22 years of experience and expertise, Dr. Sterman has conducted various phase 1 human clinical trials with gene therapy and vaccine therapy for lung cancer, mesothelioma, and other pleural malignancies.

What Dr. Sterman refers to as the “environment within the tumor” is the notion that the tumor is not just cancer cells. The tumor also contains fibroblasts, and stromal and white blood cells, and they all contribute to what Dr. Sterman refers to as an immunosuppressive environment. It’s this environment that makes it very challenging for the immune system to react and to destroy the cancer. In mesothelioma in particular, the environment inside the cancer appears to suppress the immune system more than in some other cancers.

This new understanding is allowing scientists today to go back and try once again to apply immunotherapy agents, but this time, in combination with other compounds which will work to stop the suppression of the tumor.

“It is, in fact, the ability to unblock these blocks that has led to revolution that we have today,” he added referring to the incredible progress made within the field of immunotherapy in the last 3-5 years.

Why do Vaccines Work Well for Infections, but Less Well for Cancer?

“I think there are two reasons. One is that infections like bacteria, fungi, and viruses are foreign. They’re not us. They’re not our cells,” answered Dr. Sterman.

“It is not difficult, most of the time, for the immune system to recognize a virus as different than our normal cells. But what is a cancer? A cancer is a variation of the normal cells in our body. And most of the features on the surface of the cancer cells are similar, or very close to similar, to the normal cells of our body. And our immune system is trained not to attack the normal cells in our body,” he added.

The other reason for this phenomenon is the ability of the cancer to shut down the white blood cell as it tries to fight it. Scientists are now in the process of learning why that shutdown occurs and are working to reverse it.

Moving Forward

Dr. Sterman went on to say that there are three factors from other tumors that can apply to mesothelioma in some combination and can be successful, or at least act as lessons learned:

  1. Expression of PD-L1 protein on the surface of tumor cell correlates with the likelihood of success of the anti PD-L1 immunotherapy
  2. Antibodies are not going to work if there are no white blood cells in the tumor. Infiltrating T cells must be present in the tumor in combination with a high level of PD-L1
  3. The number of abnormalities that a tumor cell has is an important factor

At this juncture, there is no definitive evidence to support that antibodies will help all patients with mesothelioma. Dr. Sterman noted that, unfortunately, tremelimumab has proven ineffective at prolonging the life of patients with mesothelioma, but he’s optimistic that a combination of approaches such as chemo and antibodies can make a difference. This also means that patients who are candidates for clinical trials should enroll in these studies, so researchers can learn best practices.

As the interview came to a close, Dr. Sterman highlighted the notion that there should be hope even though there aren’t a lot of answers and along with hope, patients should know that they have options. He emphasized that when finding clinical trials to enroll in, patients should evaluate them, see what’s available to them, and make sure they go to a center with experience in novel clinical trials. With all this newfound knowledge, what will be seen in the future of mesothelioma will be a revolution.

The full interview with Dr. Sterman is available to listen to here.

Visit our Meet the Mesothelioma Experts page at curemeso.org/experts to view information about upcoming sessions and listen to all of our past sessions.

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