Limo Chen, Ph.D.

Although immunotherapy shows great promise in improving survival for lung cancer patients, resistance to therapy is a barrier in reducing patient deaths. Immunotherapy is the use of medicines to stimulate a person's own immune system to recognize and destroy cancer cells more effectively. Some lung cancer immunotherapy targets PD-1 and PD-L1, proteins that are found on some tumor cells and immune cells. Blocking these proteins can help boost the immune response against cancer cells. In mouse lung cancer models, we have seen that the failure of anti-PD-1/PD-L1 treatment is associated with an increase in activity of a protein on the surface of immune cells called CD38. We will study the role of CD38 in resistance to PD-1/PD-L1 treatment. The findings can lead to the development of new lung cancer treatment strategies.

Update:

We have found that CD38 plays a critical role in the function of two types of immune cells, T cells and dendritic cells, which produces resistance to PD-1/PD-L1 blockade. We also found a key role for a type of tumor-infiltrating dendritic cell in maximizing the therapeutic outcome of immune checkpoint blockade, which is regulated by CD38.