I’ve been retired for 14 years. A lot has happened in medicine since then, apparently.
My latest go round with my cancer resulted in surgery, ‘radiosurgery” and now I am getting immunotherapy. The last is something that has come on since I was practicing; at least as a main-line therapy. I’m still not sure how it works. I’m getting something called a checkpoint inhibitor. The immune system is complicated. Like the blood coagulation system it appears to be like Topsy, it just grew. The clotting system consists of a number of ‘factors’ that act in various ways to cause the blood to clot by direct action and by modifying each other.
Thirty plus years ago I worked in the same laboratory as a research immunologist. He was working with melanoma cells trying to find a way to keep the immune reaction going against them, but was stymied. He wasn’t the only one. Melanoma has been of interest for many years as a potential target for immune therapy for a couple of reasons. Halo nevi are benign moles which have been targeted by our bodies immune system resulting in an area of depigmentation around the mole. This phenomenon occurs spontaneously, often following a sunburn or trauma. They can occur in conjunction with advanced melanoma or, today, in melanoma being treated with checkpoint inhibitors.
Note slight loss of pigmentation around the darker center
Microscopically, the halo nevus is surrounded by an intense lymphocytic response. These small lymphocytes are of the CD8 class of T lymphocytes. It appears that some process let the immune system know that the mole was present. Moles may become malignant and are known then as melanoma.
Rarely, metastatic melanoma goes through spontaneous regression to either absence of or much reduced disease. The mechanism is poorly understood, but it appears to be immune mediated as with halo nevi. The use of checkpoint inhibitors in melanoma today makes the study of spontaneous regression even more difficult since the checkpoint inhibitors produce the same sort of reaction posited for spontaneous regression of melanoma.
There has been an interest in the use of the body’s own immune system to fight cancer for over 100 years. One of the first attempts to stimulating the immune system involved injecting bacteria directly into tumors. The idea was that the body would recognize the bacteria and the tumor would be killed as “collateral damage”. There were a few successes, but it was largely abandoned. Today, carcinoma-in-situ of the urinary bladder is treated by injecting BCG into the bladder. BCG is an abbreviation for a bacterium.
“Bacillus Calmette-Guérin, an antituberculosis vaccine developed by the French bacteriologists Albert Calmette (1863–1933) and Camille Guérin (1872–1961).”
BCG is used in Europe in the preparation of a vaccine against tuberculosis. It is not used in the U.S. because tuberculosis can be treated with antibiotics and because the disease was a worse scourge in Europe than here. Skin tests for tuberculosis become positive with exposure to BCG which has made many infectious disease experts to discourage its use in the U.S.
Melanoma has become the poster child for checkpoint inhibitor therapy. President Jimmy Carter had melanoma with brain metastasis, and was successfully treated with checkpoint inhibitors. Treatment of other types of cancer has been successful as well. In some cases tumors are apparently eradicated, and in others reduced in size.
Why the lack of success in all tumors? That’s a good question. It appears to relate, in part, to the ability of a foreign protein on the malignant cells surface to create an immune response, and the ability of an individual’s immune system to recognize it.
For some cancers, such as the one I have, the rate of complete success is only in the 30% range, but the rate including a partial response is over 50%. While that sounds poor, the rate of success with chemotherapy approaches nil.
Cancer patients want to believe that they will be part of the lucky 30%, or the one in a hundred. Some come to believe that they are that lucky one and then are crushed when they find that they are part of the unlucky majority. I thought I might be cured by surgery and radiation until a metastasis was discovered in my brain. I was disappointed but not destroyed because I knew that my chances were about 50/50.
A simplified illustration of checkpoint inhibitors at work
I now have some understanding of how checkpoint inhibitors work – something I did not even know existed until I developed cancer – but seem to have trouble retaining the information. I would think that this might be due to the brain metastasis except for the fact that immunity is complicated, I’m in my 70s, and I haven’t really studied it.
I’ve become like my mother-in-law. She would go to the doctor and I would ask, “What did the Dr. tell you, Sue?” and she would reply, “Take one of these little green pills twice a day.” “What for? What is it?” “I didn’t ask.” She left the doctoring to the doctor, and worried herself with other things. I knew her doctor. I imagine that he was perfectly happy with her approach. I’ve always been mystified by people who didn’t want to know what they had and why they were being treated the way they were. I think my mother-in-law enjoyed being ill because it made her an object of sympathy and not knowing anything made it impossible to suggest another treatment or physician. Still, it was a problem; she claimed to have things that she didn't (ovarian cancer) and not have things that she did (hypertension).
Speaking of hypertension, a strange thing has happened. On one of my recent visits my blood pressure was 100/50. The resident told me to quit my high blood pressure medicine; that I didn’t need it. With trepidation I did. My blood pressure has gone up to normal readings. I’m still not sure what has happened. People don’t get spontaneously cured of hypertension, and I know that it was high thirty-five years ago when I started taking an ACE inhibitor, but it seems normal now. I continue to monitor it. I will feel very sheepish if I find that I never needed to take meds for my blood pressure. I have been diligent, taking my medicine on vacations, cruises; everywhere.