The Case For Combinations
One of the key principles in oncology and microbiology is that therapeutic resistance more commonly occurs with single-agent therapy than with multi-drug regimens. In fact, the development of chemotherapy regimens with non-overlapping dose limiting toxicities for the treatment of childhood leukemia still stands as the most important development in oncology serving as the exemplar in the chemotherapy age that led to the development of curative regimens in both adult and childhood acute leukemia, Hodgkin and non-Hodgkin lymphoma, and testicular cancer, as well as leading to adjuvant therapy regimens improving surgical cure rates in colon cancer, breast cancer, and lung cancer. It is conceivable that in the future development of immune-immune targeted, or immune-oncogene targeted, or immune-targeted chemotherapy regimens will become standards of care. The results from the first combined checkpoint inhibitor study, ipilimumab plus nivolumab, highlight both the promise and challenge of these types of studies.129
Clinical Trials Exploring Synergy Of Targeted Therapy And Immunotherapy
Based on the growing evidence for potential synergy of targeted therapy and immunotherapy in preclinical and murine studies, clinical trials are currently underway to evaluate these combination regimens. Early trials focused on combining BRAF-targeted therapy with cytokine-based therapy however, there are now several trials combining BRAF inhibitor-based targeted therapy with immune checkpoint blockade . Though response data are not mature on these trials and it is unclear if synergy will be seen, important information has been gained already. Namely, we have learned that complexities exist in combining these strategies, as highlighted by a clinical trial combining vemurafenib with ipilimumab . In this trial, the first cohort of patients received full dose vemurafenib at 960 mg orally twice daily for one month as a single agent prior to administration of ipilimumab at 3 mg/kg intravenously. Dose-limiting toxicity of grade 3 transaminase elevations was noted in four of six patients within 5 weeks after the first dose of ipilimumab.73 A second cohort of patients was then enrolled and treated with a lower dose of vemurafenib with ipilimumab at 3 mg/ kg. Hepatotoxicity was again observed, and the trial was closed to accrual. Of note, all hepatic adverse events were asymptomatic and were reversible either with temporary discontinuation of both study drugs or with administration of corticosteroids.73
After Chemotherapy Immune System Recovery May Be Slower Than Believed
Chemo weakens the immune system for up to nine months, especially in smokers, one study finds
Most cancer patients know that chemotherapy weakens their immune systems, putting them at risk for viral and bacterial infections.
A month or two after chemo ends, however, most people assume their immune system has returned to normal. Now, new research suggests that the effects of chemotherapy can compromise part of the immune system for up to nine months after treatment, leaving patients vulnerable to infections â at least when it comes to early-stage breast cancer patients whoâve been treated with a certain type of chemotherapy.
The small, observational study, conducted at the U.K.âs University of Leeds and Leeds Teaching Hospitals NHS Trust,also demonstrated that smoking exacerbates this effect.
âThis study has demonstrated that the adaptive immune system is altered following chemotherapy for at least nine months post-therapy,â the authors wrote in their study, published Tuesday in the journal Breast Cancer Research. âWe were surprised that the impact of chemotherapy is so long-lived.”
You May Like: Screening For Lung Cancer Uspstf
Clinical Evidence Of Immune Effects Of Chemotherapy
The concept of combining immunotherapeutic approaches with conventional chemotherapy is highlighted in the treatment of melanoma, where a number of different regimens have been tested. One of these regimens, termed âbiochemotherapyâ, has shown promise in single-center studies. Specifically, the combination of cisplatin, vinblastine, and dacarbazine was given with interleukin-2 and interferon -Î± and was associated with response rates approaching 50%.20â22 However, when randomized, multicenter studies were performed, response rates were lower and outcomes, namely overall survival, were not superior to either combination or single-agent chemotherapy23,24 Newer regimens, including nab-paclitaxel, are now being studied25 .
Cancer Itself Can Increase Infection Risk
Some types of cancer can change the way the immune system blood cells work. For instance, lymphomas , multiple myeloma, and most types of leukemia start in immune system blood cells. Other types of cancer can also affect the immune system and its cells. They can change the immune system cells so that cells that once protected your body begin to interfere with the normal way your immune system works. Cancer cells can get into the bone marrow cells where blood cells are made. The cancer cells then compete with the normal bone marrow cells for space and nutrients. If too many normal bone marrow cells are destroyed or pushed out of the bone marrow, the few cells that are left won’t be able to make enough white blood cells to help the body fight infection.
Cancer can also damage other parts of the immune system. A tumor that grows on the skin or in mucous membranes can break natural barriers and allow germs to get in. Tumors that are large might reduce blood flow to normal tissues by pressing on them or their blood supply. Tumors in the lungs may block normal mucus drainage, which can lead to infections. And, other types of tissues that have been damaged by cancer can be more prone to infections.
Read Also: How To Save Eyebrows During Chemo
What Can Go Wrong With Your Immune System
When your immune system doesn’t work the way it should, it is called an immune system disorder. You may:
Be born with a weak immune system. This is called primary immune deficiency.
Get a disease that weakens your immune system. This is called acquired immune deficiency.
Have an immune system that is too active. This may happen with an allergic reaction.
Have an immune system that turns against you. This is called autoimmune disease.
Rationale For Combination Strategies With Immunotherapy In Cancer Therapy
Though monotherapy regimens for cancer have yielded some success, there are significant limitations with regard to response rates and duration of therapy.18 Based on these limitations and some provocative preclinical evidence for potential synergy of immunotherapy with other treatment modalities,19 there is now tremendous enthusiasm for combination strategies in cancer therapy. However, rational design of these combination strategies requires a deep understanding of the effects of each therapy alone on host antitumor immunity.
Given the growing success of immunotherapy regimens across cancer types, there is significant interest in combining immunotherapeutic approaches with standard and novel agents to exploit potential synergy. The premise behind this is that several treatments may make a tumor more immunogenic, thus enhancing the effects of immunotherapy when these strategies are given in combination. Immunogenicity of tumors may be enhanced by increased antigen and MHC class I expression on tumors, but may also be enhanced by favorable changes to the tumor microenvironment . A number of therapies are currently being investigated in combination with immunotherapy including radiation therapy, chemotherapy, and a new wave of vaccines although cytotoxic chemotherapy is the prototype.
You May Like: What Happens After Chemo For Prostate Cancer
Evidence Of An Immune Response In Targeted Therapy For Other Cancers
Investigators are now exploring immune effects of targeted therapy for other cancer types. The hypothesis behind this stems from the fact that oncogenic mutations may affect anti-tumor immunity in other cancers as well. An example of this is in gastrointestinal stromal tumors , where up to 80% of tumors harbor a mutation in c-kit.75 Oncogenic mutations in c-kit lead to signaling down the MAPK and PI3K pathways, with downstream effects similar to those mediated by BRAF mutations.75
The immune effects of targeted therapy for GIST have been studied by a group from Memorial Sloan Kettering Cancer Center, which demonstrated that successful treatment with imatinib in a murine model was dependent on the presence of CD8+ T cells.76 The group also showed that the addition of immune checkpoint blockade to imatinib enhanced immune infiltrates in tumors as well as survival in the same model.76 This concept is now being studied in clinical trials for patients with c-kit mutant tumors, where imatinib treatment is being combined with ipilimumab immunotherapy . The effects of other agents are being studied in other histologies, and clinical trials are either in development or are underway.
In Built Immune Protection
This is also called innate immunity. These mechanisms are always ready and prepared to defend the body from infection. They can act immediately . This in built protection comes from:
- a barrier formed by the skin around the body
- the inner linings of the gut and lungs, which produce mucus and trap invading bacteria
- hairs that move the mucus and trapped bacteria out of the lungs
- stomach acid, which kills bacteria
- helpful bacteria growing in the bowel, which prevent other bacteria from taking over
- urine flow, which flushes bacteria out of the bladder and urethra
- white blood cells called neutrophils, which can find and kill bacteria
Different things can overcome and damage these natural protection mechanisms. For example:
- something may break the skin barrier, such as having a drip in your arm or a wound from surgery
- a catheter into your bladder can become a route for bacteria to get inside the bladder and cause infection
- anti acid medicines for heartburn may neutralise the stomach acid that kills bacteria
Certain cancer treatments can also overcome these protection mechanisms. Chemotherapy can temporarily reduce the number of neutrophils in the body, making it harder for you to fight infections. Radiotherapy to the lung can damage the hairs and mucus producing cells that help to remove bacteria.
You May Like: Low Back Pain Radiating To Groin
Some Lymphocytes And Antibodies Stayed Weak For 9 Months
For their study, the researchers monitored 88 primary breast cancer patients at various intervals from 2 weeks to 9 months after chemotherapy completion. They also had data on all but 26 of the patients before they started chemotherapy. They monitored levels of various parts of the immune system, including antibodies and a group of white blood cells called lymphocytes.
The data showed that levels of major lymphocytes, such as T cells, B cells and natural killer cells which protect against infection by viruses and bacteria fell significantly following chemotherapy.
The effect was only short term for most types of lymphocyte they returned to pre-chemotherapy levels by the 9-month mark. But the B cells and helper T cells only returned to 65% of their pre-chemotherapy levels by 6-month mark, and they were still at that level 3 months later.
B cells are important for producing antibodies, and T helper cells assist in that task. Antibodies are important for helping the immune system identify and eliminate pathogens like viruses and bacteria. There are different antibodies for different pathogens.
What Is Coronavirus Or Covid
Coronaviruses are a large family of viruses that are common in people and many different species of animals. SARS-CoV-2 is a novel coronavirus that causes a respiratory disease named coronavirus disease 2019, which is abbreviated COVID-19.
As SARS-CoV-2 spreads, the virus can change, which results in new variants. Some variants may spread more easily than others or be more resistant to vaccines or treatments.
Also Check: Things To Do During Chemo
Avoid People Who Are Sick
People with a weak immune system should avoid being too near to anyone who has a cold or another infection.
Viruses and other infectious illnesses can spread from person to person through close contact. They can also spread in the water droplets that a person expels into the air when they cough or sneeze.
It is not always possible to avoid people who are ill. However, a person with a weak immune system should always avoid close contact, such as hugging or kissing, with the unwell person until the illness resolves. They should also avoid sharing food and beverages with the person.
The Type Of Cancer Treatment You Have
Chemotherapy reduces the number of white blood cells produced by the bone marrow. This can have a big effect on the immune system. It reduces your body’s defences against infection during and after treatment. Chemotherapy treatment is usually the most common reason for reduced immunity.
You are particularly at risk of getting an infection 7 to 14 days after having chemotherapy, when the level of white blood cells is at its lowest. This time is called the nadir. It can vary slightly depending on the drugs used.
The number of white blood cells will increase steadily and usually returns to normal before your next cycle of chemotherapy.
You will have your blood checked before you have more chemotherapy, to make sure the white cells are at a normal level. Your chemotherapy nurse will give you more information.
Surgery can make you more at risk of infection. This is because it makes a break in the skin or in the mucous membranes, which both help protect the body from infection.
If the operation involves removing the spleen, infection is much more likely. The spleen is an important part of the immune system. It contains white blood cells that fight infection and gets rid of old red blood cells. Having your spleen removed means that your immunity is permanently affected. Your doctor will advise you to take low-dose antibiotics for the rest of your life, to protect your from infection.
Also Check: Can You Survive Ovarian Cancer
You May Be Moderately Or Severely Immunocompromised If You
- are currently receiving treatment for cancer
- had an organ transplant and are taking medicine to suppress the immune system
- had CAR T-cell therapy or a stem cell transplant within the last 2 years
- are taking high-dose corticosteroids or other drugs that may suppress the immune system
- have a moderate or severe primary immunodeficiency syndrome
- have advanced or untreated HIV infection
If you recently received cancer treatment that suppresses the immune systemsuch as chemotherapy, a stem cell or bone marrow transplant, or cell therapyyour doctor may suggest that you wait until your immune system has recovered before you get vaccinated. Or your doctor may suggest that you wait a few weeks after vaccination to get immunosuppressive treatment.
CDC also recommends that people who received one or more doses of COVID-19 vaccine before or during a stem cell transplant or CAR T-cell therapy be revaccinated with an mRNA vaccine for any dose received before and during treatment. Revaccination should start at least 3 months after transplant or CAR T-cell therapy.
Talk with your doctors if you think you may need to be revaccinated.
Learn more about what people with cancer should know about COVID-19 vaccines. To find a COVID-19 vaccine near you, visit Vaccines.gov.
Breast Cancer Treatment And Your Immune System
Some cancer treatments, such as chemotherapy, affect the immune system making it harder for the body to fight infections. This can increase the risk of becoming seriously ill if you get Covid-19, although being fully vaccinated is the best protection against serious illness due to Covid-19.
However, not all cancer treatments affect the immune system.
Also Check: Good Gifts For Someone Going Through Chemo
Cutting Edge: Targeted Therapy Effects On Immune Microenvironment
Over the past 15â20 years, numerous oncogenic mutations have been described in cancer that contribute to their malignant potential through increased growth and invasiveness, resistance to apoptosis, and increased angiogenesis.42 Treatment of cancers with pharmacologic agents targeting these mutations represents one of the most significant advances in cancer therapy in decades, and these forms of therapy may demonstrate high response rates but are often limited by a relatively short duration of response.43 This is highlighted in melanoma, where pharmacologic inhibition of the BRAF oncogene results in responses in the vast majority of patients.44,45 However, responses to therapy are of limited duration, with most patients progressing on therapy within a year. Numerous molecular mechanisms of response and resistance to BRAF-targeted therapy have been identified,39,46â56 and there is now growing evidence that there may be immune mechanisms of response and resistance57â60 as well, providing a potential avenue to improve responses by combining molecularly targeted therapy with immunotherapeutic approaches.
Different Treatments Different Impacts
Because cancer treatments attack the disease in different ways, they may also affect the immune system in different ways. For instance:
Chemotherapy drugs are designed to kill fast growing cells, which most cancer cells are. But chemotherapy may also attack fast-growing healthy cells, such as those found bone marrow, which produces immune cells, hampering their ability to protect you from illnesses, bacteria and other threats.
Surgery, especially major surgery, may put a burden on the immune system, exhausting its reserves to help prevent infection and heal wounds caused by the procedure. Surgery requires cutting through the skin and layers of tissue, which may expose the body to germs. Also, surgeons may need to remove lymph nodes, which help fight infection.
Radiation therapy works by exposing cancer cells to ionizing waves of energy that kill the cells or stunt their growth. While destroying or damaging cancer cells, the treatment may also damage healthy cells and contribute to conditions that may lead to an increased risk of infection.
Immunotherapy drugs called checkpoint inhibitors are designed to boost the immune system by helping them to better recognize and attack cancer cells. But, in some cases, an overactive immune system may attack healthy cells and cause flu-like symptoms or potentially serious autoimmune conditions, such as colitis.
Recommended Reading: Can Chemo Affect Your Eyes
Too Few Fruits And Veggies
These foods may help your body make more of the white blood cells you need to fight off infections. Fresh produce and nuts and seeds pack a lot of zinc, beta-carotene, vitamins A, C, and E, and other nutrients you need for a healthy body. Plant-based foods also fill you up with fiber, which helps lower your body fat percentage, which can strengthen your immune response.