Essential genes combat cancer

The immune system can be programmed to attack cancer, but it doesn't always work, and doctors work out why.
14 August 2017

Interview with 

Nicholas Restifo, NIH


Cancer cells in culture


A cancer treatment known as "immunotherapy" has the potential to revolutionise the way we treat/manage malignant diseases. It involves programming the immune system to attack and remove cancer cells from anywhere in the body. It's at an early stage but some people with life-threatening cancers have been cured by the technique. For others, though, the treatment has failed, so doctors want to know why. And now we have a clue, because scientists in the US, by painstakingly deactivating each of the genes in a cancer cell, have discovered which genes need to be working to make the therapy effective. Nicholas Restifo led the study and he's based at the NIH in Maryland…

Nicholas - For the immune system to see the cancer, the cancer must be able to present itself as foreign to the immune system. And the cancer requires the expression of particular genes and, if those genes are not present, the immune system simply cannot see the cancer. We systematically knocked out all protein encoding genes within the human genome and we found there were about 100 genes that were essential for the immune system to recognise tumours.

Chris - Have you gone a step further and said well, if we go and take cancer cells from a patient who has not responded to immunotherapy can we indeed see that this 100 or so genes that you’ve found to be critical are messed up or broken in that patient's cancer, thus explaining why they haven’t responded to the immunotherapy treatment?

Nicholas - Yes. We analysed over 11,000 patients with cancer and we correlated gene expression that we found using our screen with those patients, and we found very interesting overlaps with that dataset. In addition, we took about 200 patients that had received immunotherapy. Some of them responded to the immunotherapy and some of them didn’t. We are particularly interested in the patients who did not respond and, yes indeed, we found that many of those patients had problems in the genes identified in our screen.

Chris - Does this mean then that you have in your hands potentially quite a powerful prognostic tool because you could take a tumour from somebody, you could see if it has this constellation of 100 or so genes that are necessary intact, and then say well, the chances of you responding to immunotherapy pretty good or, if they’re broken, those genes, the chances of you responding are less good?

Nicholas - Yes, that’s a very interesting and important question. The dataset that we have now will enable us to make a guess what the best kind of therapy is for a patient.To give an example: if we have a particular kind of white blood cell from the patient that needs to recognise particular structures on a tumour cell that simply aren't there, then that patient might benefit from a different treatment. So yes, the dataset could guide us towards picking the patients that will ultimately benefit but, most importantly, the dataset might help us create new drugs or new work-arounds. So, if the immunotherapy that we’re using to treat a patient has something missing then we can potentially provide that signal to the patient so that the immune approach that we’re using can still succeed.



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