Cancer Immunotherapy on the Cusp

Editor’s note: Immunotherapy is a type of cancer treatment that uses a patient’s own immune system to fight cancer. Immunotherapies work in multiple types of cancer, but they have been particularly successful in treating melanoma. This article gives a good overview of the current state of immunotherapy research.

“Glass crystals with thread-like filaments floating inside sit in the offices of two prominent immunologists. The clear blocks encase models of the structure of PD-1/PD-L1, a receptor-ligand pair that rides on the surface of cells, ready to rein in the immune system after its work attacking invaders is done.

“PD-1 looms large in the growing field of cancer immunotherapy, which is why one model appears on Gordon Freeman’s desk in the Dana-Farber Cancer Institute and the other in Arlene Sharpe’s office at Harvard Medical School. Their basic science discoveries about how cancer cells hijack PD-1 to turn off the immune system are being translated into therapies that they hope and believe can change cancer treatment. After 15 years, drugs developed by several pharmaceutical companies based on the scientists’ work are awaiting approval by the U.S. Food and Drug Administration.

” ‘It’s coming,’ Freeman, HMS associate professor of medicine at Dana-Farber, said this summer, anticipating FDA action.”

Molecular Pathways: Co-Expression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy

“The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include CTLA-4 (Cytotoxic T Lymphocyte Antigen-4), PD-1 (Programmed Death-1), LAG-3 (Lymphocyte Activation Gene-3), TIM-3 (T cell Immunoglobulin and Mucin protein-3) and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that co-expression of checkpoint molecules occurs frequently on cancer-specific T cells, as well as on pathogen-specific T cells in chronic infections. While the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of pre-clinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through non-overlapping molecular mechanisms. Here we review current data regarding immune checkpoint molecule signaling and co-expression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins.”