Funded by the Constellation Gold Network Distributors
Diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, can often be cured with chemotherapy. However, DLBCL will relapse in ~40% of patients. When this happens, currently available treatments are usually not effective. Treatments for relapsed DLBCL also cause many side effects that affect quality of life. Programmed death-1 (PD-1) blockade immunotherapy has been very effective in treating a number of human cancers, and is generally well-tolerated by patients. Unfortunately, PD-1 blockade therapy has not been very effective for patients with relapsed DLBCL. Therefore, we need to define biological markers that identify DLBCL patients who are likely to benefit from this type of treatment. In search of such a marker, we found that DLBCLs with an increased number of genes for the partner of PD-1, known as programmed death-ligand 1, were associated with strong evidence that an immune response had been generated against them. We will now test whether lymphomas with PD-L1 gene duplications will be more likely to shrink after treatment with PD-1 blockade therapy, and we will also attempt to determine what other features of these lymphomas are important in determining whether the immune system can recognize them. We expect that the knowledge gained from our studies will improve outcomes for patients who have DLBCL that has relapsed.