James P. Allison

tissue because they're just doing what, that's their normal function is to protect tissue and help it heal. They just happen to, you know, they get in a weird situation where they are treating the tumor like a wound and protecting it from the immune system.

tissue because they're just doing what, that's their normal function is to protect tissue and help it heal. They just happen to, you know, they get in a weird situation where they are treating the tumor like a wound and protecting it from the immune system.

So that's one of the things that we're working on now is trying to find out some way to override that or change the myeloid cells where they'll help. They could also help the T cells. It just depends on what they're doing. It's a whole new area of biology that

So that's one of the things that we're working on now is trying to find out some way to override that or change the myeloid cells where they'll help. They could also help the T cells. It just depends on what they're doing. It's a whole new area of biology that

that single-cell RNA techniques and things are making us realize that when you talk about T cells, you know, there used to be B cells and T cells. Now they're T cells specifically. First there were two kinds, then there were five kinds. Now there are about seven kinds. The truth is that Those kinds are just constructs that we make up. In biology, it's a continuity. It's just a continual spread.

that single-cell RNA techniques and things are making us realize that when you talk about T cells, you know, there used to be B cells and T cells. Now they're T cells specifically. First there were two kinds, then there were five kinds. Now there are about seven kinds. The truth is that Those kinds are just constructs that we make up. In biology, it's a continuity. It's just a continual spread.

In myeloid cells, it's really pronounced. You can see all these different cells. They differ by two or three genes that are being expressed. And you can just shift the population one way or another. And that's what we're trying to figure out. And then shift them from this protective overall effect to the helping one. a thing to help the immune system rather than hinder it.

In myeloid cells, it's really pronounced. You can see all these different cells. They differ by two or three genes that are being expressed. And you can just shift the population one way or another. And that's what we're trying to figure out. And then shift them from this protective overall effect to the helping one. a thing to help the immune system rather than hinder it.

Yeah, which genes are turned on and how much, and it's the relative amounts of different genes in some cases. The complexity is amazing, and so... You know, our brains cut and box things, but nature doesn't.

Yeah, which genes are turned on and how much, and it's the relative amounts of different genes in some cases. The complexity is amazing, and so... You know, our brains cut and box things, but nature doesn't.

Well, yeah. I mean, in the 70s, nobody knew what the T-cell receptor was. I mean, that was my first thing when I got into immunology was, what is the antigen receptor? What is it that the T-cell uses? And nobody knew what it was. And so I put on my biochemist hat and said, well, what should such a molecule look like? And worked it out and published that for the first time in 82.

Well, yeah. I mean, in the 70s, nobody knew what the T-cell receptor was. I mean, that was my first thing when I got into immunology was, what is the antigen receptor? What is it that the T-cell uses? And nobody knew what it was. And so I put on my biochemist hat and said, well, what should such a molecule look like? And worked it out and published that for the first time in 82.

it's going to look like this. And I had data and stuff. And then the genes were cloned a couple of years later and confirmed that that's what it was, an alpha chain, a beta chain, two chains of protein, both of which have constant regions and then variable regions. That's how they give you the combining site. But how is it presented? And so there was this

it's going to look like this. And I had data and stuff. And then the genes were cloned a couple of years later and confirmed that that's what it was, an alpha chain, a beta chain, two chains of protein, both of which have constant regions and then variable regions. That's how they give you the combining site. But how is it presented? And so there was this

I won't go into the details too much, but that's another complicated thing, how the molecule, that hot dog, it doesn't, you know, every wiener won't fit into that bun. You know, everybody's bun's a little bit different. It holds a different kind of wiener. And so, you know, if you've got the right, you know, bun for the peptide, you can present it. If you don't, you won't.

I won't go into the details too much, but that's another complicated thing, how the molecule, that hot dog, it doesn't, you know, every wiener won't fit into that bun. You know, everybody's bun's a little bit different. It holds a different kind of wiener. And so, you know, if you've got the right, you know, bun for the peptide, you can present it. If you don't, you won't.

So, you know, that's another, if you can't present a peptide, even though it's there and it's from a cancer, then the T cells aren't going to see it.

So, you know, that's another, if you can't present a peptide, even though it's there and it's from a cancer, then the T cells aren't going to see it.

Okay, well, I won't go anymore, but it's a complicated thing. But we didn't know this stuff until the 80s and the 90s, and now we're beginning to understand in some detail. And now, with a lot of the work in terms of really understanding the biology of it, some of this...

Okay, well, I won't go anymore, but it's a complicated thing. But we didn't know this stuff until the 80s and the 90s, and now we're beginning to understand in some detail. And now, with a lot of the work in terms of really understanding the biology of it, some of this...