Empowering a patient's own immune system to clear away tumors

Immunogenetics: Open access journal focuses on the genetic research areas of autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease, diabetes mellitus type 1, systemic lupus erythematous, etc.

Immunogenetics is the branch of medical genetics that explores the relationship between the immune system and genetics.

Now that we know why some patients don't respond as well to immunotherapy, we can begin developing more informed approaches to treatment decisions for instance, developing predictive algorithms to determine a person's likely response before initiating immunotherapies that may have a high probability of not working or working poorly for them.

Cancerous or infected cells wave molecular flags that tell the immune system to clear them away before the problem gets out of control. The flag poles molecules of the Major Histocompatibility Complexes (MHC) are displayed at the surface of most cells in the body. MHCs hold up antigen flags bits of just about everything from inside the cells and display them to immune cell surveyors that are constantly checking for damaged or infected cells. Since tumor cells carry a lot of mutations, they show up frequently among these flags, allowing the immune system to detect and eliminate them.

Sex and age differences have long been observed when it comes to immune response. For example, females have twice the antibody response to flu vaccines and are far more susceptible to autoimmune diseases. Similarly, human immune systems tend to weaken as we age. But if females and younger people have stronger immune responses in most cases, you might expect cancer immunotherapy to work better for them, not worse.

To get to the bottom of this conundrum, Carter's team looked at genomic information for nearly 10,000 patients with cancer available from the National Institutes of Health's The Cancer Genome Atlas, and another 342 patients with other tumor types available from the International Cancer Genome Consortium database and published studies. They found no age or sex-related differences in MHC function.

What they did find was that, compared to older and male patients with cancer, younger and female patients tend to accumulate more cancer-causing genetic mutations of the sort that MHCs can't present to the immune system as efficiently. This is likely because robust immune systems of the young and female are better at getting rid of cells displaying well-presented mutant self-antigens, leaving behind tumor cells that rely more heavily on the poorly presented mutations. This selective pressure is known as immuno-editing.

This shows an important thing, that the interplay between the cancer genome and the adaptive arm of the immune system is not a static one. Two simple but important variables, age and sex, influence this interplay.The study also emphasizes the master role of the MHC in dictating the outcome of this interplay, reaffirming its central role in the evolution of disease, cancer included, at the level of the individual and population.

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Contact Details
Robert Solomon
Managing Editor
Immunogenetics: open access