Cancer Immunosurveillance Comes of Age

The study of how the immune system recognizes friend and foe, or as the immunologist Sir Macfarlane Burnet phrased it, “distinguishes between self and non-self,” has driven important discoveries that are transforming our ability to treat cancer.

Over the last century, scientists and clinicians have unraveled the complex interactions (both in innate and adaptive immunity) that lead to the eradication of viruses, bacteria, parasites, and now, cancer. Notable cellular players include T cells, B cells, natural killer (NK) cells, neutrophils, eosinophils, basophils, dendritic cells, and macrophages, along with a host of secreted mediators —antibodies, complement, cytokines, and chemokines — each of which fulfills particular immunologic functions.

When the immune system fails to regulate these processes, autoimmune disease can be a consequence. These diseases also occur if shared antigens are recognized by the immune system in normal and in cancer cells; one example is Lambert-Eaton syndrome. Monoclonal antibodies that target tumor reactive T cells (eg, nivolumab and pembrolizumab) can also cause autoimmune disease; other examples include graft-vs-host disease (GVHD) in allogeneic bone marrow transplant recipients and cytokine release syndrome (CRS), which is associated with adoptive T cell therapy.

Through the efforts of thousands of investigators, starting with Dr William Coley over a century ago and more recently including researchers such as Drs Macfarlane Burnet, Lewis Thomas, Steven Rosenberg, Carl June, James Allison, and Lloyd Old,^1-7 oncologists can now offer patients effective US Food and Drug Administration (FDA)-approved immunotherapy treatments designed to directly or indirectly attack cancer.

Historical timeline for FDA approval of representative immunotherapy and related drugs and selected indications:^8,9