"Dennis Lyon was a genetic train wreck. Cancer was ravaging his liver lungs bones and brain and tests showed so many tumor mutations that drugs targeting one or two wouldnt do much good. It seemed like very bad news yet his doctors were encouraged. The reason People with the most messedup genes often are the ones who do best on treatments that enlist the immune system. These are the patients we used to be very depressed about thinking they couldnt be helped said Dr. Razelle Kurzrock at the University of California San Diego. Now when we see those types of patients were really excited because there are so many ways for the immune system to recognize the cancer cells as abnormal. Immunotherapy is the hottest thing in cancer care. Drugs called checkpoint inhibitors can vanquish some advanced cancers by removing a chemical cloak that hides them from the immune system. Former President Jimmy Carter got one at age  for skin cancer that spread to his brain and now is in remission. But theyre expensive have side effects and work for only about onequarter of patients  as few as  percent with colon cancer and as many as half with the skin cancer melanoma. Sometimes the benefits are brief. AP VideoCindy Sharp  Worst of all For a small number of unlucky folks treatment can backfire. Their cancer grows exponentially after getting a checkpoint drug. Were going to have to figure out not only who to treat with immunotherapy but who not to treat Kurzrock said. Gene tests are starting to help sort that out. But for patients the big question is Will it work for me PREDICTING WHO BENEFITS The first step is testing for a protein called PDL thats often involved in forming that chemical cloak. Some checkpoint drugs target this or a related protein so people with a lot of it should respond to treatment. That was the hope when Diane Tippett showed up last October at Georgetown Lombardi Comprehensive Cancer Center with a salivary gland cancer that had spread to her liver and lungs. Five years ago I probably would have thrown up my hands and given her standard chemo said the centers director Dr. Louis Weiner. Instead he ordered tests that showed Tippett had a PDL mutation meaning her cancer made a lot of it. He started the yearold Leonardtown Maryland woman on a checkpoint drug Opdivo and told her to come back in a few months. Quite honestly I didnt know if Id ever see her again he said. Now Tippetts lung tumors are gone. Her liver tumor shrank  percent and is stable. She got married in July and says she feels great. I dont feel any different than you do. Im not tired Ive got all my hair she said. I want more people to know about it and to ask their doctors about it she said of immunotherapy and the testing that led her to it. NOT THE WHOLE STORY That protein isnt a very reliable predictor though. Some people with a lot of it dont benefit from the drugs and the opposite also is true. There are other checkpoints besides that one too. Researchers increasingly are focusing on something else Tippett had a high number of flawed genes. Its a sign that tumors have been evolving over time and are hard to treat with drugs that target a single gene. It sometimes accompanies two other DNA problems that some checkpoint drugs already are approved to treat. Lyon the San Diego man had nearly two dozen different mutations after his skin cancer spread widely. In October  he started on Opdivo and was in nearcomplete remission within two months. Recent tests showed no active cancer in his spine and lungs and doctors think small spots in his brain and liver may be scar tissue though they cant know for sure. A test for tumor DNA in his blood found none. It would appear my cancer is all dead he said and called it nothing short of miraculous that gene tests led to successful treatment after years of trial and error. Im so grateful. No ones lucky that gets cancer but I may be in an era where theres a way through this tunnel. Threequarters of patients who are helped by checkpoint drugs have longlasting benefits as Lyon did said Dr. Steven ODay an immunotherapy expert at Providence Saint Johns Health Center in Santa Monica California. When you respond its a home run in terms of longterm survival ODay said. But we still have to be better at predicting who those patients are. THE DARK SIDE Others have not been so fortunate. In November French researchers reported httpdx.doi.org..CCR that  of  patients or  percent got much worse after checkpoint drugs which seemed to speed their tumor growth. Kurzrock checked with colleagues and quickly found more cases  a yearold man with bladder cancer a yearold woman with endometrial cancer and a yearold breast cancer patient whose tumors just exploded in size within two months of immunotherapy. In a report httpdx.doi.org..CCR on  patients she tied several gene mutations to this risk. Kurzrock has consulted for some genemedicine makers and cofounded a company using a software program to determine best treatments for patients depending on their tumor genes. The unfortunate cases are a reality check said Dr. Len Lichtenfeld deputy chief medical officer of the American Cancer Society. We are not paying close enough attention to those people and need to know whether they fared badly because of their treatment or for other reasons he said. SHOULD WE BE DOING IMMUNOGRAMS Thats the question Dr. Eric Topol director of the Scripps Translational Science Institute posed a gene medicine conference he organized in March at the suburban San Diego research center. Should there be baseline tests to map what patients natural defenses look like For example how many immune system soldiers called T cells do they have in the area of the tumor Max Krummel is working on a roadmap to do that. The University of California San Francisco scientist heads a project with  million from three companies that make checkpoint drugs. He is analyzing hundreds of tumor samples to see what immune system features spell success or failure. Were not looking at how the immune system changes but for what starting point works best with the drugs he said. What were seeing is that the kinds of cells you have in a tumor predict whos going to respond. Krummel who was involved in work that led to Yervoy the first checkpoint drug has started a company to try to tune up one part of the immune system he thinks is key to maintaining a healthy balance. Cancer exists because the immune system isnt working as it should he said so successful immunotherapy may require treating the immune system not treating the tumor."