Thank you. And then, also, happy Halloween, right? Everyone has a plan tonight, probably, and it's definitely the only day of the year I can get away with a jacket like this. I thought I would take the opportunity, and so I thought I would also start with a Halloween-appropriate slide. This hopefully will have some meaning to you. All of us hope that when we give a lecture that people in the audience remember just one thing, and that would be enough, and that's more than most of us can say about lectures we listen to. So if you remember one thing, it's this. That's the thing, but it will have some meaning at the end, I hope.
Okay, I thought I would talk about the research that we do, which seeks to target what we call the cancer glycocalyx. And glycocalyx is a word that means the coating of complex carbohydrates that every cell enjoys. And I'll try to convince you that the cancer glycocalyx could be playing a role in the ability of cancer cells to evade recognition by the immune system, and conversely, we might be able to intervene in that process by targeting the glycocalyx with therapeutic modalities.
You know, most people, certainly in this audience of chemists and biologists, have heard about cancer immunotherapy as an exciting new advance in our ability to treat cancer. You really can't go anywhere without gaining some exposure to the excitement surrounding this. If you read journals like Science and Nature, you'll see every now and then the cover dedicated to this subject. And I think Science, you know, gave cancer immunotherapy the Breakthrough of the Year award, and Nature's been talking about it. If you're at the bookstore, you might find books about it. When you're at the supermarket, stuck in line at Safeway, you might notice it's on the cover of Newsweek and the cover of Time.
And I really love this cover because it kind of makes it sound like it's like an episode of Game of Thrones or something like that, you know, the brutally selective, hugely expensive, life-saving trials of immunotherapy. Wow, you know, who doesn't want to read that? That's pretty cool. And then, oh, New Scientist, this is kind of provocative. So New Scientist went so far as to name immunotherapy cancer's penicillin moment. Wow, right? I mean, if you think about what that implies. And then, of course, the cynic in me had to go on Google and Google cancer and penicillin moment, and it turns out cancer has had five penicillin moments in the last 20 years. Okay, so, you know, I don't know, so we'll see, right? We'll see. But it's certainly exciting times.
And, you know, I think probably the person who did more than any of these outlets to popularize the notion of using the immune system to target cancer would be our own former President Jimmy Carter. So you might remember a few years back, he had an awful diagnosis of metastatic melanoma in his brain. And at that time, or prior to that time, that was surely a death sentence. I mean, that was a horrible prognosis associated with that. But he was fortunate that, you know, his diagnosis came at a time when he could go on one of the recently approved immune therapies. And he was lucky because he was one of the about 20% of patients with that diagnosis that actually shows a response. So, you know, he may well have been cured, which is kind of like a retrieval from the grave, quite honestly, for people who would have that kind of a diagnosis.
So to frame what I'm going to talk about with the glycocalyx, I thought it might help to start by talking about the drug that Jimmy Carter took and how it works. And all of those drugs target a particular synapse between immune cells called T cells and cancer cells. But it turns out that T cells, they also have receptors, for example, one called PD-1, another called CTLA-4, that deliver inhibitory signals to the T cell, and they'll keep the T cell quiet. And if there's enough of these inhibitory signaling molecules that get recruited to the synapse, they can kind of overpower the activating signal coming from the T cell receptor.
So the T cell is doing a calculation where it's looking for signs of badness, signs of goodness, which is what these ligands would be, and deciding how to react. And so it shouldn't surprise people to learn that a successful tumor often has evolved molecules that send the signal of goodness, of health. And so knowing all of that, you know, people coming from the backgrounds of immunology and oncology figured out how to intervene, right? If you could block the signal between those negative or inhibitory signaling receptors and their ligands, then you could basically tilt the equation in favor of the activating receptor and allow it to deliver an activating signal, so the T cell will then kill.
Well, it turns out that there's a long history of literature that correlates altered glycosylation and cancer, and some of that literature includes things like poor clinical prognosis, right, or inability to respond to certain kinds of chemotherapeutics. And it's a really old literature. So, you know, these papers were being published before I was born, which is like, you know, 35 years ago or so. But anyways, it's been a long time, and it's a very frustrating body of literature to try and digest because it's almost exclusively correlative with very little in the way of a mechanistic explanation.
So we know that if you compare the signature of glycosylation from healthy cells and cancer cells, there's differences, and they're quite stereotyped for certain types of cancer. But what does that mean for the actual progression of disease, and what do those glycosylation signatures actually contribute to the process of cancer? You know, there really hasn't been much to say in that regard. And then about, you know, I'm going to say like 10 years ago, Max, a picture started to emerge, and it came courtesy of the human genome sequencing project, like so many other things, and the identification of a family of receptors in humans that are now called the Siglec family.
So Siglec is an acronym. It stands for sialic acid binding immunoglobulin superfamily lectin-like molecules. And there's 14 of them in human, and then nine of the 14 have that domain I pointed to on PD-1, the ITIM domain. We now know that virtually all classes of leukocytes, so every cell in your immune system, expresses Siglecs, sometimes more than one. So these are widespread in the immune compartment, and they have the ability through their ITIM domains to recruit SHIP phosphatases. And I just told you hypersialylation is a common phenotype on malignancies.
So if you put all that together, it kind of begs the question, the answer to which I think is sort of hiding in plain sight, which is: do Siglecs function as checkpoint receptors in the context of tumor immune evasion? Or is the reason so many cancers are hypersialylated due to the fact that that could be a survival adaptation that protects them from immune surveillance, just like having PD-L1 would protect against T cell activity? So about six years ago, we started working on this, and we thought we would test this hypothesis experimentally, starting with a focus on NK cells, which are a type of white blood cell or leukocyte that, you know, is thought to be important in protecting us against cancer.
