Dr. Herbst on Immune Resistance in Lung Cancer

Roy S. Herbst, MD, PhD
Published: Monday, Nov 12, 2018



Roy S. Herbst, MD, PhD, chief of medical oncology, professor of medicine, at Yale Cancer Center, Smilow Cancer Hospital, discusses mechanisms of immune resistance for patients with lung cancer.

Only about 15% to 20% of patients with lung cancer derive significant benefit from immunotherapy, and there are several reasons why patients develop resistance to this treatment approach, Herbst says. The main reason is that they have “cold” tumors—their tumors are not inflamed and are without T cells.

For those 50% to 60% of patients, researchers need to find ways to bring immune cells into the tumor. Herbst suggests T cells can be attracted with cytokines through the use of biospecific antibodies or other agents can be used to modulate the tumor microenvironment to make it more favorable.

Additionally, there are some tumors that do not use PD-L1 as the primary checkpoint. If researchers can gain a better understanding of other checkpoints that may be involved, they could potentially use other agents such as TIM-3 or LAG-3 to improve response.

Herbst notes that there are still some patients whose tumors have all the favorable qualities—such as T cells and PD-L1 expression—yet they still do not respond to immunotherapy. While immunotherapy has changed the way thoracic oncologists treat lung cancer, many questions remain in this space.


Roy S. Herbst, MD, PhD, chief of medical oncology, professor of medicine, at Yale Cancer Center, Smilow Cancer Hospital, discusses mechanisms of immune resistance for patients with lung cancer.

Only about 15% to 20% of patients with lung cancer derive significant benefit from immunotherapy, and there are several reasons why patients develop resistance to this treatment approach, Herbst says. The main reason is that they have “cold” tumors—their tumors are not inflamed and are without T cells.

For those 50% to 60% of patients, researchers need to find ways to bring immune cells into the tumor. Herbst suggests T cells can be attracted with cytokines through the use of biospecific antibodies or other agents can be used to modulate the tumor microenvironment to make it more favorable.

Additionally, there are some tumors that do not use PD-L1 as the primary checkpoint. If researchers can gain a better understanding of other checkpoints that may be involved, they could potentially use other agents such as TIM-3 or LAG-3 to improve response.

Herbst notes that there are still some patients whose tumors have all the favorable qualities—such as T cells and PD-L1 expression—yet they still do not respond to immunotherapy. While immunotherapy has changed the way thoracic oncologists treat lung cancer, many questions remain in this space.



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