Hoogland Lymphoma Biobank

Immunotherapy in Cancer Treatment: the Development of Immune Checkpoint Blockade Therapies

Immunotherapy is revolutionizing the treatment of cancer. Many patients are now able to live longer and with less side effects compared to conventional chemotherapies. At the forefront of the immunotherapy movement is the development of immune checkpoint blockade therapies, most notably programmed death-1 (PD-1) receptor blocking antibodies which reactivate cancer-specific immune responses that have been inhibited by programmed death-ligand 1 (PD-L1) expressed on the surface of cancer cells. Anti-PD-1 antibodies have shown activity across cancer, and have remarkably provided long-term survival in a subset of patients. For example, 34% of patients with melanoma are alive 5 years after starting a PD-1 inhibitor, and the 5-year survival was quadrupled amongst patients with advanced non-small cell lung cancer.

Despite these impressive results, the overall response rates to these treatments are quite low on the order of 10-30% in most cancers. Moreover these therapies are amongst the most expensive prescribed medications in the world, and with rising health-care costs a more effective way of predicting which patients will benefit from immunotherapy are needed. We have therefore initiated a study using lymphoma patient samples from the Hoogland Lymphoma Biobank at The University of Chicago Comprehensive Cancer Center to help identify predictive biomarkers of response to immunotherapy.

Specifically, we are now evaluating whether the presence of PD-L1 gene amplification can represent a novel biomarker to help predict which patients will benefit from anti-PD-1 antibodies. PD-L1 gene amplification is present across cancer and strongly correlates with the expression of PD-L1 on the tumor surface. PD-L1 amplification therefore appears to be an important method in which cancer cells avoid destruction by the immune system. We believe however that reactivating the immune system with immunotherapies such as anti-PD-1 antibodies will lead to excellent outcomes in these patients. We are therefore investigating whether PD-L1 amplification can be used as a valuable biomarker to predict response to anti-PD-1 antibodies for a number of cancers. Ultimately, we hope these studies will improve patient outcomes and deliver more cost-conscious care, and we are very thankful to the Hoogland family for their help in the support of our research missions.

James Godrey MD, 2017-2018 Hoogland Fellow