Chemotherapy-induced Immunosuppression

A discussion with researcher Heather Zwickey, PhD

By Natural Medicine Journal

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Nearly all patients receiving broad-based chemotherapy will experience immunosuppression. Chemotherapy, by design, targets rapidly dividing cells. It does not discriminate between cancer cells and other rapidly dividing cells. Since immune system cells divide quickly—especially during an immune response—they are among the many targets of chemotherapy. This is the reason that patients receiving chemotherapy are more prone to infections. The biggest clinical outcomes of immunosuppression are bacterial, viral, or fungal infections. Another side effect can be chemotherapy-induced long-term fatigue, which may have a cytokine etiology.
Heather Zwickey, PhD, recently presented at the Oncology Association of Naturopathic Physicians (OncANP) annual conference on the topic of immunosuppression in patients undergoing chemotherapy. Natural Medicine Journal talked to Zwickey about this important oncology topic.

Q. Has immunosuppression improved since the introduction of new chemotherapy drugs or the use of combination chemotherapy drugs?

A. The use of new chemotherapy drugs, specifically the monoclonal antibodies, has reduced but not eliminated chemotherapy-induced immunosuppression. And unfortunately, drug-resistant variants of the cancer commonly develop after treatment with some of the so-called “targeted therapies.” So, while these drugs elicit surprisingly fast cancer regression, long-term success with them can be less than ideal.
There are very new drugs, some of which are still in clinical trials or have just been released on the market, that stimulate the immune system, specifically, sipuleucel-T and ipilimumab. However, even with these drugs we see some immunosuppression. This reinforces what we’ve known for decades—namely that the tumor itself can be immunosuppressive. Thus, only a subset of patients responds to these drugs.

Q. What can patients and practitioners do to help reduce the chance of immunosuppression?

A. Unfortunately, nothing can be done in this regard. In fact, if you tried to stimulate the immune system during chemotherapy, you would likely make the immunosuppression worse. As the immune system is stimulated, the cells divide more quickly, and this makes them more likely to be killed by the chemotherapeutic agent.
If a patient is on one of the immunostimulatory drugs, further stimulating the immune system could be favorable—although this hasn’t been studied yet. Cancer immunologists are currently writing theory papers about it. For example, sipuleucel-T is a dendritic cell (DC)–based vaccine. Further stimulating DC activation, which happens with herbs like Oregon grape root (Mahonia aquifolium), could enhance the vaccine’s effects; however, no evidence has yet confirmed this.

Q. Once the patient’s immune system is compromised, are there things that can be done to rebuild the immune system? If so, what would be a few key strategies?

Naturopathic medicine is ripe with ways to bring back the immune system, especially when you recall that 70% to 80% of the immune system is in the gut. There’s not a lot of literature on rebuilding the immune system post chemotherapy, specifically. However, we know from the malnutrition literature that a balanced diet is very important to bringing back immunity. Considering protein, vitamins, minerals, and trace elements is essential when trying to rebuild cell populations. Promoting a healthy gut with probiotics, glutathione, and healthy fats (polyunsaturated) is also going to be important.
There’s a lot of research suggesting that acupuncture could be beneficial for reducing immunosuppression. In fact, there are now funded clinical trials studying this therapy.

Q. Where would you like future research to focus on in this area?

A. I’m not a fan of chemotherapy because chemotherapy shuts down the very system that I study. Focus should be placed on validating some of the promising treatment approaches that do not include chemotherapy.
My first priority with respect to cancer research is to find funding for a non-chemotherapeutic novel treatment for breast cancer. There’s a surgeon in La Quinta, California, who uses a modified military digital infrared system to detect breast cancer, and then applies cold needle ablation to destroy the tumor. The whole visit can be completed in the office with local anesthesia. The physician has completed a case series of more than 500 patients, and it’s time to do a clinical trial. If the clinical trial shows the same results as the case series, it will revolutionize how breast cancer is treated. However, the clinical trial would be large and complex. And finding funding for research that doesn’t support mainstream treatment is difficult.
I’m also interested in applying the “positive deviant” strategy to cancer. Positive deviants are the people who have the best results—often orders of magnitudes above others with the same diagnosis. The strategy is to determine what the positive deviants do, and then study that. We see many cases of positive deviants in cancer—those with so-called “spontaneous remission” for example. Spontaneous means that we just don’t understand it yet. If we did understand it, could we replicate it? There is really so much that needs to be done in this area.

About the Expert

Heather Zwickey, PhD, earned a PhD in Immunology and Microbiology from the University of Colorado Health Sciences Center with a focus on infectious disease. Zwickey went on to complete a postdoctoral fellowship and teach medical school at Yale University. At the National University of Natural Medicine in Portland, OR, Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developing programs in research, nutrition, and global health, among others. She currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences worldwide. At Helfgott Research Institute, Zwickey applies her immunology expertise to natural medicine, with specific interest in the gut-brain axis in neuroinflammation.  

About the Author

Natural Medicine Journal is an electronic peer-reviewed journal and open access website dedicated to the field of integrative medicine.