Illustration: MARTIN JARRIE
Pecking away at the mystery of cancer immunity
While genes can dictate obvious human characteristics, from blue eyes to curly hair, this array of genes on chromosome 6 is especially important for less-visible reasons.
The activity of these genes, known collectively as major histocompatibility complex genes, or MHC genes, determines whose donor tissues will match if a patient needs an organ transplant.
photo Markie RamirezMarcia Miller
People whose cells feature similar MHC proteins, such as a sibling or twin, can donate tissue without the recipient’s immune system recognizing it as foreign. But MHC genes do even more: They help protect against infectious diseases and may influence the growth of cancer.
Marcia Miller, Ph.D., professor in the Division of Molecular Biology, has studied this bewilderingly complicated gene family at City of Hope for 26 years — not in humans, but in chickens, which feature a similar array of genes.
“Chickens have been a very important experimental model for years,” said Miller. “We know about B-cells and T-cells because of studies of chickens” — which also have taught scientists a lot about how cancer develops.
What makes one hen in the chicken coop “unique” may seem like an exotic question, but Miller believes that understanding how MHC genes vary from chicken to chicken could reveal how the human immune system recognizes some cancer cells as foreign and then kills them.
In a recent study in the Journal of Immunology, Miller identified chicken MHC genes she believes may protect birds from cancer. That cancer is a fatal form of T-cell lymphoma called Marek’s disease, which is caused by the highly contagious Marek’s disease virus, or MDV, a member of the herpes virus family.
In humans, herpes viruses cause diseases ranging from benign warts to cancer. Immunocompromised AIDS patients can develop at least two herpes virus-related cancers: Kaposi’s sarcoma and AIDS-related lymphoma.
Interestingly, though, some chickens infected with MDV never develop cancer. They appear no different from uninfected birds, apparently because genes within their MHC complex suppress tumor growth. No one has identified these genes, but Miller is on the case.
When Miller and her colleagues figured out the sequence of DNA in areas next to the “core” chicken MHC genes, they found genes that might account for cancer resistance.
Among these were genes that encode a protein found on the surface of natural killer cells, special immune cells that kill cells that have been infected by viruses or are cancerous. They also found other unique genes that hold the recipe for proteins associated with other virus-fighting activities. Given that so many of the genes identified are related to immune response, Miller predicts that at least one is responsible in part for MHC-conferred resistance to Marek’s disease. Some researchers believe the genes in question reside in another section of DNA, but she believes the story is more complex.
“The door is still open that it could be genes in this other region,” she said. “And we think we know which one.” Ongoing studies in her lab should determine whether she is right.
Grants from the National Science Foundation, the National Cancer Institute and the United States Department of Agriculture funded the research.