Self & Other · Cancer and the Immune System

What Else Is Being Tried

Within weeks, her cancer was gone. It is, as of this writing, still gone. Emily Whitehead is now in her late teens, doing the ordinary things teenagers do, alive because of a treatment that did not exist when she was born and that her doctors were not sure would work even as they were preparing to give it to her. The CAR-T therapy that saved her was approved by the FDA in 2017, the first cell therapy ever approved in the United States, and tens of thousands of patients have now received it for various B cell cancers. Other CAR-T therapies have been approved since, for other cancers. The landscape of treatment for some blood cancers has been redrawn in fifteen years.

As with checkpoint inhibitors, the limits are real. CAR-T cells have so far worked best against cancers of the blood and bone marrow, and have struggled against most solid tumors — the cancers that make up the bulk of human cancer disease. The engineering challenges are large. The treatment is expensive. The side effects, especially cytokine release syndrome and certain neurological complications, can be severe. The research has not yet solved the problem of the solid tumor.

But the proof of principle is now in. T cells can, when properly engineered, find and destroy cancer cells in a way that is sometimes curative. The question is no longer whether the immune system can be turned against cancer. The question is how to extend what already works against some cancers to the many cancers that are still untreated by these methods.

What Else Is Being Tried

Two more developments are worth mentioning briefly, because they may shape the next decade of cancer treatment.

The first is personalized cancer vaccines. Every cancer has its own particular set of mutations, and those mutations produce particular mutant proteins that, in principle, the immune system could be trained to recognize. Modern sequencing makes it possible, after a tumor is biopsied, to identify the specific mutant proteins (called neoantigens) that are unique to that patient’s cancer, and to design an mRNA-based vaccine that teaches the patient’s own T cells to attack any cell carrying those neoantigens. Several trials, including some involving the same mRNA technology that produced the COVID vaccines, have shown promising results in melanoma and pancreatic cancer in particular. Personalized vaccines are not yet standard of care for any cancer. They are, however, being tested seriously, with results that suggest they may add real benefit on top of checkpoint inhibition.

The second is the older but still important domain of vaccines that prevent cancer entirely by preventing the infections that cause it. We mentioned the HPV vaccine in Chapter 4 — it prevents most cervical cancers, and several other cancers, by preventing the human papillomavirus infections that drive them. The hepatitis B vaccine prevents liver cancers caused by chronic hepatitis B infection. These are not cancer immunotherapy in the modern sense; they are old-fashioned vaccinations that happen to prevent cancers because the cancers are caused by viruses. But the cancers they prevent are real, common, and often lethal in their advanced forms. The HPV vaccine, in particular, is on track to eliminate cervical cancer as a meaningful public health problem in the populations that vaccinate consistently. This is, in its quiet way, one of the great achievements of modern cancer prevention.

What This Has and Has Not Changed

It is important, before we leave this chapter, to be clear about what the cancer immunology revolution has done and what it has not.

What it has done: it has given oncologists a class of treatments that, for some cancers and some patients, can produce durable complete responses where previous treatments produced only delays. Five-year survival in metastatic melanoma, which was around five percent before checkpoint inhibitors, is now approaching half. Some children with previously incurable leukemia are now in long-term remission after CAR-T. The standard of care has changed in dozens of cancers in the last decade. Patients who would have died are alive.

What it has not done: it has not cured cancer. Many patients do not respond to immunotherapy. Many cancers still have poor prognosis. The treatments are expensive and not equally available everywhere. The success stories are real. They are not the whole story.

The honest summary, for a young person reading this book, is something like: cancer is still a deeply serious disease, and the best advice for any individual cancer is still to find a good oncologist, follow good evidence, and ask hard questions. But the field has changed in ways that make some cancers, in 2025, dramatically more survivable than they were in 2005. The immune system, the same system that has been the subject of the previous eleven chapters, is now part of the toolkit. It was always there. It just took us until very recently to learn how to use it.

There is a passage in the writings of Lewis Thomas, the physician who first articulated cancer immunosurveillance in the 1950s, in which he speculates that the immune system probably catches and eliminates many cancers throughout a lifetime, that we never know about most of them, that the cancers we do see clinically are the ones that broke through. He could not prove this in 1959. He could only argue for it.

We can, more or less, prove it now. The immune system does watch for cancer. It does eliminate, quietly, an unknown but substantial number of cells that have begun to turn malignant before they can ever become diseases. The cancers we see in clinics are the ones that escaped. And the most exciting development of the last fifteen years is that, for some of those escaped cancers, we have learned how to put the immune system back on the case — by removing the brakes, by engineering the cells, by teaching the system what to see.

This is not the end of the story. It is something more useful: a chapter that has clearly turned. The William Coley intuition that almost destroyed his career has, a hundred and thirty years later, been vindicated in the strangest possible way — by a Texas immunologist studying T cell brakes, by a Japanese researcher who started by looking at cell death, by a six-year-old in Pennsylvania whose engineered T cells nearly killed her before they cured her, by a former president who lived a decade more on a drug whose mechanism his attending physicians could not have explained when he was sworn in for the first time.

The next chapters of the book turn to a different question. We have spent the first half of this book talking about how the immune system works, and the middle of the book talking about what happens when it goes wrong. In the second half, we turn to a more practical question: given the system we have, what can a person actually do to live well with it? What helps? What only sounds like it helps? What, despite everything we have just covered, will not protect anyone from anything? The lifestyle conversation is full of misinformation, and the next chapter is going to try to clean it up. Carefully. Honestly. Without telling anybody to drink a green juice.

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