Augmenting the Immune System to Achieve Great Outcomes in Cancer Care

During the session "Principles of Immunotherapy" at the National Comprehensive Cancer Network 20th Annual Conference, Anthony J. Olszanski, RPh, MD, from the Fox Chase Cancer Center, described the complex interplay between the immune system and cancer.

He began with a basic explanation of the history of immunotherapy and how because cancer commonly grows from our cells, the immune system often considers them as “self” and does not reject the cancer.

Since all cancers inevitably result in a genetic defect at some point, the immune system is then able to differentiate and recognize the antigens being produced by the cancer cells.

“So even though tumors are ‘self,’ they have mutations,” Dr Olszanski said. “Those mutations are producing proteins either in over-expression or mutation, which might be able to express an antigen presenting itself as non-self antigen. Very important.”

He then went on to highlight a recent article in New England Journal of Medicine by Snyder et al¹ that found melanoma patients with more than 100 mutations had a better survival rate compared with patients with less mutations.

Dr Olszanski also described the immunoediting hypothesis, which helps to explain why cancer progression can occur so differently in patients. There is the illumination phase, in which active immune surveillance recognizes the tumor and eradicates it; the equilibrium phase, where the cancer is not growing as quickly because there is a balance between tumor progression and the immune system trying to suppress that progression; and, finally, the escape mechanism, where either reduced immunogenicity prevents the immune system from finding the cancer effectively or the cancer grows faster than the immune system can suppress it.

“So the immunoediting hypothesis really helps explain how some of our patients seem to do exceedingly well, might get complete remissions, and never come back; other patients seems to have stable disease; and other patients seem to escape it completely,” he explained.

He went on to describe some of the immunotherapies currently out there that are expanding knowledge of both the immune system and diseases. For instance, PD-1 inhibitors has captured a lot of attention because they have been widely useful in a variety of cancers, such as the use of nivolumab in non-Hodgkin’s lymphoma bringing about some reduction in the tumor burden of every patient, he said.

In addition, the PD-L1 antibody, MEDI4736, has shown activity in a wide variety of cancers, including pancreatic cancer.

“Can we imagine another therapy option for our pancreatic cancer patients who have to go through the chemotherapy that we currently give them today?” he asked. “If immunotherapy works in that patient population, I can say that we’ve really made some headway against one of the most devastating diseases that we currently have out there.”

¹Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371:2189-2199