Many Americans were introduced to the concept of immunotherapy when former President Jimmy Carter was successfully treated for brain cancer, in his nineties. This groundbreaking approach to cancer therapy mobilizes the patient’s own immune system to kill the tumors in his or her body. Immunotherapy is in its infancy, and its success depends upon increasing scientific understanding of the human genome.
Scientist Eduard Porta-Pardo, Ph.D. is the lead author of a study recently published in the journal Cancer Immunology Research. The study was conducted by the Sanford Burnham Prebys Medical Discovery Center (SBP). The researchers have identified over 100 previously unknown genetic regions that affect the body’s immune response to malignancy. Dr. Porta-Pardo explains:
By analyzing a large public genomic database, we found 122 potential immune response drivers — genetic regions in which mutations correlate with the presence or absence of immune cells infiltrating the tumors. While several of these correspond to proteins with known roles in immune response, many others offer new directions for cancer immunology research, which could point to new targets for immunotherapy.
With immunotherapy, it is possible to treat even tumors that have metastasized to other organs. Several immunotherapy drugs currently in use have shown remarkable success eradicating or dramatically shrinking cancerous tumors, and in some cases, preventing a a recurrence.
The mechanism used by immunotherapies is assisting the immune system in recognizing the cancer as a threat, and permitting the infiltration of the tumor by immune cells. In many cases, tumors “hide” from the immune system, or block entry of immune cells into the tumor in ways scientists do not yet understand.
The senior author of the study is Adam Godzik, Ph.D., professor and director of the Bioinformatics and Structural Biology Program. He says:
To develop immunotherapies that are relevant to a wide range of cancers, we need to know a lot more about how the immune system interacts with tumors. Our study provides many new leads for this endeavor.
This work emphasizes the value of open data, because we could access genomic data from over 5,000 tumor samples from The Cancer Genome Atlas (TCGA), we could jump straight to analysis without having to set up a big collaborative network to gather and sequence so many samples.
Our plan for the next phase of this research is to use this algorithm to search for genetic regions correlating with the levels of specific immune cell types within the tumor, which will reveal further details of cancer immunology.
Dr. Porta-Pardo adds:
We are exploring cancer mutations at fine resolution by accounting for the fact that mutations can affect the encoded protein in different ways depending on where the resulting change is located, Our algorithm, domainXplorer, identifies correlations between a phenotype, in this case the amount of immune cells in the tumor, and mutations in individual protein domains — parts of a protein with distinct functions.
After generations of treating cancer with chemicals that injure healthy tissue as they attack tumors, and weaken the patient’s immune system so that his body cannot defend itself independently, it may be that medicine has found a new way forward.