Last week we discussed the importance of host immunity in survival of the cancer patient and how we evaluate that immunity.
Now we want to briefly tell you what we do with that information about a cancer patients immune system.
Cancer vaccines may be used as additional (adjuvant) treatment after completion of the standard of care therapy to help prevent cancer recurrence, or in a combination with chemotherapy and sometimes radiation in the Stage IV patients.
After the patient completes standard of care therapy which may be a combination of surgery, chemotherapy and radiation all of which are immunosuppressive; they should be rested 3-4 months before the immune system is tested. (Please see the previous blog on Understanding your immune system on July 19, 2017 for the blood tests we use to evaluate a person’s immune system.) If a patient has a depressed lymphocyte immunity, an adjuvant cancer vaccine is indicated.
The use of a cancer vaccine in a Stage IV patient can be done, but the timing of the vaccine depends on other treatment protocols. For instance, what type of chemotherapy cycle and is radiation involved? The type of drugs used in chemotherapy are very important, as some complement immunotherapy by causing cancer cells to die an immunogenic cell death. This promotes better tumor cell antigen presentation to dendritic cells that then drain to the lymph nodes to stimulate effector T-cells. The vaccine is timed and given during the chemotherapy cycle based on parameters to be discussed later.
Sometimes a great immune cascade occurs causing marked tumor reduction and a tremendous host response.
Now that we have discussed the importance of evaluating a cancer patient’s immune system before any treatment is started, we will discuss the specific blood tests we use to get a detailed summary of a person’s immune system.
Complete Blood Count (CBC) – this blood test gives information on a person’s red blood cells (RBC), white blood cells (WBC), and platelets. The red blood cells carry oxygen to all parts of the body. White blood cells are the cells that fight off infection. There are several types of white blood cells, and each has a unique purpose. Chemotherapy usually makes the white blood cells very low. The platelets help with clotting to prevent too much bleeding when someone hurts themselves.
Total Serum Immunoglobulins (IgG, IgM, IgA, & IgE) – this blood test measures several antibodies in the blood that are responsible for defending us against infection. Each immunoglobulin or antibody has a certain job such as IgA tends to help fight infections throughout the entire gastrointestinal tract and in the lungs. IgG has the ability to enter certain tissues to fight infections. IgE is associated with allergic reactions. IgM is the first one on the scene of an infection and also helps stimulate other immune cells to fight off foreign bodies.
Lymphocyte Phenotyping– the most common lymphocytes are the T cell and the B cells. The T cell has several subtypes of cells that help stimulate a person’s immune system to fight infection or a foreign body. The B cell makes antibodies and can help stimulate more T cells to help fight infection or foreign bodies.
Lymphocyte Blastogenesis Assay (LBA) – this assay determines if a patients immune system can recognize certain cancer proteins or even a patient’s own cancer. It is helpful to have a small sample of the person’s actual cancer to put in this test to determine if a person’s immune system can determine the cancer is a “foreign body”.
These blood tests help us in understanding your immune system. We can figure out if the immune system has the components to adequately put up a “fight.” We ultimately want to make the body think the cancer is a foreign body and to fight it. Most cancer’s disguise themselves and fly under the radar of the immune system and that’s why they can grow and spread throughout the body. Our immune system is constantly fighting every day.
At our center, our goal is to help boost the immune system so it can fight off cancer.
As we have previously written, most patients with cancer are treated with some combination of either surgery, chemotherapy, or radiation treatment. The patient’s immune system is often ignored during the current treatment of cancer. We have published numerous papers on the importance of studying and treating the cancer patients immune system also know as host immunity.
As previously published in an editorial in 2005, a cancer patient’s immune system should be evaluated before any treatment is started. There are several ways to measure the immune system and measure the response of the immune system after treatment (Elliott et al., 2005):
DTH (delayed-type hypersensitivity)
Proliferation assays
Chromium release assay
Elispot
Cytokine flow cytometry (CFR)
Tumor antigen peptide tetramer-binding assay
Clinical observation of response
It is important to determine if a cancer patient has an overall good immune system, especially to their own tumor-associated antigens (TAA). If a patient has a good immune system and their immune system is able to recognize their tumor, then they have a better outcome (Head et al., 1993). This concept applies not only to breast, but several cancers including lung, stomach, pancreas, and colon.
Our research as well as previous studies support the finding that evaluating a cancer patient’s immune system before, during, and after treatment is important to determine if there was a response to treatment. Two independent researchers decades apart demonstrated the positive relationship between a person’s immune system and survival. Riesco et al., 1970 demonstrated that measuring a cancer patients total lymphocyte count before treatment could determine a patient’s survival. Fumagalli et al, 2003 also showed how a cancer patient’s lymphocyte count determines their overall survival.
At our center, we believe in supporting a cancer patient’s immune system. In our cancer patients, we measure a total immune profile and a lymphocyte blastogenesis assay. These two tests give us detailed information on a cancer patients own immune system including the number of T cells and B cells which are important cells to fight infection and cancer. These tests also lets us know if the cancer patient’s immune system can recognize certain cancer markers. In some cases, we are actually able to see if a cancer patient’s immune system can recognize their own cancer!
While we are a breast center, we see and treat patients with other cancers. Our goal is to help support a patient’s immune system so that they can use their own immune system to help fight off their current cancer and prevent any recurrence of cancer. We believe immunologic therapy can compliment traditional treatment for cancer, but evaluating a cancer patient’s immune system is important and should not be ignored!
Stay tuned……..more to come on understanding a cancer patient’s immune system!
Robert L Elliott M.D., Ph.D.
Catherine Baucom M.D., Ph.D.
REFERENCES:
Elliott RL & Head JF. 2005. Host Immunity Ignored in Clinical Oncology: A Medical Opinion. Cancer Biotherapy & Radiopharmaceuticals. 20(2):119.
Head JF, Wang F, Elliott RL, et al. 1993. Assessment of Immunological competence and host reactivity against tumor antigens in breast cancer patients: Prognostic value and rationale of immunotherapy development. Ann NY Acad Sci-Fi. 690:340.
Riesco A. 1970. Five-year cancer cure: Relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 25:135.
Fumagalli LA, Vinke J, Hoff W, et al. 2003. Lymphocyte counts independently predict overall survival in advanced cancer patients: A biomarker for IL-2 immunotherapy. J Immunotherapy. 26:394.
A cancer treatment that has recently received a lot of attention in medical reports and even to the public by TV ads. Some great results have been achieved in some patients, but in my opinion there is still much to be done. We are still too much involved with treating the disease and often forgetting the host with the disease. Many believe cancer immunotherapy is a new modality, but as you will see later in this and future posts, the concept has been around for quite some time.
In 2005, I published an editorial entitled “Host Immunity Ignored in Clinical Oncology: A Medical Opinion.” At that time, I emphasized the importance of host immunity cancer survival. Cancer immunotherapy was still considered experimental and was not part of the Big Three Cancer Treatments: (1) Surgery, (2) Chemotherapy, and (3) Radiation; all of which are in themselves immunosuppressive and damage the host’s immune system.
There is now much attention on cancer immunotherapy, but this attention is on patients that have metastatic Stage IV disease. Why don’t we support the immune system early in the disease and in the early stages of standard of care therapy? After completion of therapy, why don’t we evaluate the patient’s host immunity? If there is specific depressed lymphocyte immunity to the patients own tumor; why don’t we then offer an autologous vaccine to that patient in the adjuvant setting?
This vaccine may be what is needed to delay or prevent recurrence. We have done that in a group of patients that had depressed lymphocyte immunity to their own tumor after standard of care therapy. Those patients were vaccinated with an autologous vaccine containing their modified cancer cells, proteins, and biologic adjuvants targeted to their own tumor. The results were published in 2012 and showed the vaccine improved disease specific survival in the vaccinated patients. This vaccine was for breast cancer, but this technology will probably be beneficial solid epithelial tumor.
Our vaccine stimulates the adaptive immune system, while most of the newer therapies are passive immunity. We will explain in later posts, but these are monoclonal antibodies given by infusion to a certain tumor target. Checkpoint inhibitor drugs are similar and are targeted to immunosuppressed elements in the tumor microenvironment. These are great and help patients with metastatic disease. The point is why don’t we try harder to prevent metastatic disease and eliminate the need for expensive other cancer immunotherapies? This would be cost effective and much better for the cancer patient and their families.
In upcoming posts, I will explain the types of cancer immunotherapy in more detail, and also other measures that can be done to support the immune system during therapy. We will emphasize things neglected, what you should look out for and how you might improve your odds. I will quote some passages from our papers on the subject. Hope you enjoy and get something from this post; and we eagerly await your comments and questions.
