The science behind Cancer Immunotherapy

Continuing a discussion from another thread:

In post 16 of that thread we read the incredible story of @Ani99 (Kyrani Eade), who experienced a spontaneous remission of stage 4, metastatic ovarian cancer:

In Sydney I was diagnosed with stage 4 ovarian cancer with metastases to the uterus, cervix, bowel and both lungs. AND type 2 diabetes as there were high blood sugars. “Nothing we can do for you” they said. I wasn’t about to give up on my life so I went to a Chinese herbalist and I believed back then that they helped because by early 1994 after more tests the doctors found no evidence of disease. I really believed that the Chinese herbs cured me but a decade later I realized that I must have had a spontaneous remission of the cancer the first time.

For those who do not know me, I am a PhD immunologist. You can read my bio at the end of this article that I recently wrote here for BioLogos about vaccine safety. I currently work in the field of immuno oncology, so I thought readers on this Forum might enjoy some links that I could give you about this field of research at the intersection of oncology and immunology, which has led to new clinical medicines.

Although spontaneous cancer remissions are rare, they are known to happen.
Kyrani’s story reminded me of a couple patient experiences described by oncologist, Steven Rosenberg, MD-PhD, which led him to believe that the immune system could be harnessed to fight cancer.

I became very interested in this when I was a resident in surgery at the Peter Bent Brigham Hospital in Boston, where I ran into two extraordinary cases that had a considerable impact on me.

One was a fellow with stomach cancer that had spread to his liver and other places. He was operated on, but beyond that there was no treatment for him. Miraculously, 11 or 12 years later he was completely disease-free. He had undergone one of the rarest events in medicine and that is the spontaneous regression of metastatic cancer. At the time, this was only the fourth reported case of a stomach cancer with spontaneous regression in the absence of treatment and it seemed to me that the immune system was the likeliest suspect for having caused that.

The second was a patient who had been treated several years earlier and had undergone one of the early kidney transplants at the Peter Bent Brigham Hospital. It turned out that the kidney that was put into the patient inadvertently and unknowingly harbored cancer. Kidney function returned after the transplant, but the patient then developed widespread renal cancer.

When he was taken off of immunosuppressive drugs—which were preventing the transplanted kidney from being attacked and rejected by the immune system—his cancer disappeared. Of course, he also lost the kidney, but it demonstrated that even advanced, widely metastatic cancers could be eliminated with a strong enough immune reaction. Although it involved reaction against tissue from another person, this case showed that it was possible, that the immune system was powerful enough to cause cancer regression.

Those two patients profoundly influenced me in my pursuit of immunotherapy. Those efforts then continued in 1974 when I moved to the National Cancer Institute at the National Institutes of Health.

Since then, many other immunologists have entered the field of Immuno Oncology or Cancer Immunotherapy. Another example is Robert Schreiber, PhD:

And the researchers, James Allison, PhD and Tasuku Honjo, M.D., Ph.D., were awarded the 2018 Nobel Prize in Medicine for their research which led to the drug development of “checkpoint inhibitors” which stop “breaks” that hold back the immune system. Inhibitors of CTLA4 (ipilimumab) and PD1 (nivolumab, pembrolizumab) are now used in the treatment of cancer.

This is all just one example of how observations and scientific study can lead to advancements in the treatment of human health.

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Thank you for your work and for sharing. I have a good friend 5 years out from stage 4 melanoma with complete remission due to immunotherapy through M.D. Anderson, and of course Jimmy Carter has done well with a similar story.

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The kidney was destroyed by the immune system as it was foreign, so with it the cancer was gone. If he had had the kidney from a donor that was a twin and the kidney was a genetically identical I don’t believe that the immune system would have destroyed the cancer.

What evidence is there that the immune system destroys cancer cells? I would be grateful if you can give me any studies that were done to show the immune system involvement in destroying cancer. I am not convinced by anything I have seen. And if it does, then why is the immune system instrumental in cancer progression and metastasis?

The links I put in the top post highlight many studies done and drugs designed to encourage the immune system to fight cancer. Those professors and many others within the field have conducted numerous studies.

In Steven Rosenberg’s seminal work, for example, he originally treated cancer patients with high dose IL-2, which expands T cells (an immune cell type that has cytolytic properties). Later on in his career, his group dissected melanoma tissues from which they could expand T cells (tumor infiltrating lymphocytes, TILs) out of the tissues in the lab using IL-2 and then transfer the T cells back into the patients to cure some patients. This was an example of a new type of therapy called “Cell Therapies” or which the media often calls “Living Drugs.”

Where I work now, we are engineering T cells to improve their properties for these types of treatments

In addition to TIL therapy, there are other types of cell therapies were we can add receptors called chimeric antigen receptors (CAR) that increase the ability of the T cells to recognize certain type to make a CAR-T cell

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In most solid tumors around 50% of the cells on average are actual cancer cells the rest are epithelial or stromal cells. And of the cancer cells there are many heterogenious subpopulations. If immunotherapy targets only a small number of cells how is it that people see tumors shrink? What about the stromal cells? Wouldn’t they survive and thus there would still be a tumor?

IMO immunotherapy has to be another placebo effect like the early years of chemotherapy drugs targeting the rapidly dividing cells in cancer. People saw tumors shrink and even disappear entirely, yet there are no rapidly dividing cells in cancer.

I do not understand why the presence of stromal cells is concerning to you. The stromal cells are not malignant. Either they die off due to lack of support, or they go back to areas of normal, non malignant tissue.

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That is not true for all cancers, some are and some aren’t, which is why there are different treatments for different cancers. Not every cancer is treated with chemotherapy. I had a slow growing tumor in my parotid gland below my ear, which a doctor misdiagnosed as an enlarged lymph node. It grew very slowly, getting almost imperceptibly larger for 10 years until it started causing some pain so I finally decided to get a second opinion. Chemotherapy was not recommended, surgery was, and it was malignant so good that I got it out before it became metastatic

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Did you read any of the links it the top post? As I noted above, rare spontaneous remissions are known to occur, likely due the the immune system mounting an effective anti-cancer response.

Placebo affects are perceptible in some instances, I also believe in the power of prayer. But importantly, I also understand the value of prospective controlled clinical trials. The dramatic effects of certain immunotherapies against particular cancers is not a placebo affect.

See this incredible story about science saving a life:

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An informative book about cancer is The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee. It was the basis of a Ken Burns film not so long ago.

And there are free/cheap (but excellent) college courses on coursera.org

Finally, for highschool students, there are resources on biointeractive.org

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Quite a poignant story!

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Looking to see if PBS had it streaming (they don’t), I found this interview:

Yes the Emperor of All Maladies PBS show was excellent! The book did not talk about cancer immunotherapy, because the field took off only recently, after the book was published. However, Episode 3 is all about immunotherapy, and was great!

Although the episodes are not streaming for free they can be purchased (I bought my copies on iTunes) are worth the price

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Your library probably has it.

here is the official trailer

Good that you had it removed. May you have good health from now on.
Parotid gland is the largest of the salivary glands, which means they are involved with digestion. May I please ask you, did you have any anxiety or worry at that time? If it was slow growing then the anxiety or worry, if present, would have been intermittent or low grade over time. .

I zero anxiety prior to my nephrectomy. Have you seen my account, by any chance?

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Biomedical researchers are focused on the cancer cells and I can understand that but they are not there in isolation. One of the reasons why chemotherapy fails is because stromal cells protect the cancer cells so there is drug resistance.

In my stage 4 cancer I can assure you there was no immune system attack of the cancers. I would have had inflammation in all areas if that was the case and I had none.

But even apart from that the immune system works together with the cancer cells for metastasis to take place and here too the stromal cells are involved. If cancer cells were to really hi-jack the immune system then there would have to be an unbelievable amount of “evolution” in the time it takes for the cancer to develop. At least a half dozen or more new proteins and/or new protein functions would have to come into being. And what about in sarcomas

This is high level involvement by the immune system cells. I don’t see how it can possibly be that the cancer cells hi-jack the immune system cells. There is co-operation and maybe from early on in the cancer niche.

Yes I got the book but I am not impressed by it.
I am writing a book on cancer too. I am calling it "The Emperor of All Maladies is Just A Paper Tiger!
There is foul game play and related, inhumane people behind cancer. So I would define cancer as “stem cell mediated immunity, erroneously ignited in the body owing to false beliefs”. I found that when you understand what is involved you can resolve the problem, no need for any medicines whether alternative or mainstream. I don’t advise people on treatment. That is their business but I can advise on spontaneous remission of cancer deliberately brought about.

Dogs get cancer also, at about the same rate as humans, and certain breeds have a predisposition to developing certain types of cancer. Is this because of the dogs’ false beliefs?

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