Understanding Cancer Immunoediting Will Aid Vaccine Development

The body’s immune system employs the process of cancer immunoediting to eliminate tumor cells bearing highly antigenic mutant proteins and to suppress growth of those cancer cells that lack these antigens.

Cancer immunoediting, the process by which the immune system controls tumor outgrowth and shapes tumor immunogenicity, is comprised of three phases: elimination, equilibrium, and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. To understand better the molecular basis that drives immunoediting, investigators at Washington University School of Medicine (St. Louis, MO, USA) induced the formation of sarcomas in a line of immunocompromised mice.

The investigators then used massive parallel DNA sequencing to characterize mutations expressed on the sarcoma cells, which were phenotypically similar to unedited primary tumors growing in immunocompetent hosts.

Results published in the February 16, 2012, issue of the journal Nature revealed that the genome of the sarcoma cells contained 3,743 mutations. Using class I prediction algorithms, they identified the protein produced by the mutant spectrin-beta2 gene as a potential rejection antigen of the sarcoma and validated this prediction by conventional antigen expression cloning and detection. They also demonstrated that cancer immunoediting occurred via a T-cell-dependent immunoselection process that promoted outgrowth of preexisting tumor cell clones lacking highly antigenic mutant spectrin-beta2 and other potential strong antigens.

“The idea would be to make a vaccine that helps the immune system recognize and attack six or seven of these mutated proteins in a cancer,” said senior author Dr. Robert Schreiber, professor of pathology and immunology at Washington University School of Medicine. “Therapeutically, that could be very helpful.”

“Many of the cancer genome projects now under way are looking for the “driver” mutations, or the mutations that cause the cancers,” said Dr. Schreiber. “Our results suggest there may be additional information in the sequencing data that can help us make the immune system attack cancers. Until very recently, this work would have been impractical because of the costs involved, but the technology has improved and prices have come down, and now it is possible to obtain this genetic information for a few thousand dollars instead of a million.”

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Washington University School of Medicine