Generally speaking, cancer is a colony of body cells that gets out of control, drains the body of resources, and spreads to other parts of the body through the bloodstream | Photo credit: Getty Images
Cancer, often referred to as the “emperor of all diseases,” remains a formidable foe despite decades of scientific progress. However, research in recent years has brought us closer to unlocking new ways to fight back. A study from Northwestern University in Chicago, published in the November issue Journal of Clinical Investigationhas gained attention for the discovery that white blood cells activated by severe COVID-19 show cancer-fighting abilities.
Working with laboratory mice, researchers have shown that the spread of cancer, also known as metastasis, can be slowed by a special type of white blood cell called non-classical monocytes (I-NCMs). These cells can be produced through a severe infection like COVID-19 or through the use of certain chemicals. Once activated, I-NCM can leave blood vessels and migrate to tumors, where they can attack cancer cells. COVID-19 is known to cause worse consequences for the elderly and those suffering from diseases including cancer. However, there have been rare reports of cancer going into remission (no disease) after COVID-19.
A 2023 study by De Nigris and colleagues in Journal of Translational Medicine described 16 such cases involving various types of cancer, including leukemia, lymphoma, myeloma, and kidney cancer. However, it is not clear whether these results are directly caused by COVID-19 or are part of the natural progression of the disease. This raises the question: Can cancer go away on its own? When it’s rare, the answer is yes. The best-studied example is neuroblastoma, a childhood tumor that sometimes disappears without treatment. The spontaneous improvement may be due to the newly activated immune system gaining the ability to target cancer cells.
The potential of immunotherapy
Over the past decade, immunotherapy has emerged as a promising approach to cancer treatment.
Generally speaking, cancer is a colony of body cells that gets out of control, drains the body of resources, and spreads to other parts of the body through the bloodstream. Cancer cells often reprogram the body’s immune system to protect themselves from detection and destruction, like thieves bribing security guards to look the other way. Immunotherapy aims to overcome these defenses by strengthening the body’s immune cells to fight back. Northwestern University research shows that injecting a specific type of white blood cell, I-NCMs, into mice is effective in fighting cancer metastasis.
I-NCMs are derived from monocytes circulating in the bloodstream. Monocytes are involved in fighting infection, immune regulation and repairing damaged tissue. When exposed to infection or certain bacterial or viral chemicals, some of these monocytes transform into I-NCM. If the white blood cells represent all the adults in a city and the monocytes are the people who can choose the military, think of the I-NCM as the chosen few of the military who qualify for special commando units.
Unlike regular monocytes, I-NCMs have a unique receptor, CCR2, which acts like a specialized antenna to detect signals emitted by certain types of cancer cells or inflammatory tissues. The signal guides the I-NCM to the source, where it performs a specific task. For example, at the site of infection, it helps eliminate pathogens. At the tumor site, they recruit other immune cells called natural killer (NK) cells, which effectively destroy cancer cells. Natural killer cells are an important component of the immune system, directly targeting and eliminating cells that appear abnormal, such as cancer cells or cells infected with a virus. Unlike T cells and B cells, natural killer cells do not require prior approval from the body’s adaptive immune system. This ability to act quickly and decisively makes them a critical part of the body’s innate immunity. They work as a front line defense against infection and cancer.
A Northwestern University study found that I-NCM plays an important role in inviting these NK cells to tumor sites. So how did this special I-NCM come about? Researchers have found that infections like COVID-19, caused by the SARS-CoV-2 virus, can cause this formation. However, this does not mean that all patients with COVID-19 will experience an increase in cancer outcomes. Bacterial products like peptidoglycan and NOD2 agonists such as MDP (muramyl dipeptide) analogs can also be used to convert normal monocytes into I-NCM.
Breakthroughs over the years
The idea of using the immune system to fight cancer is not new. At the end of the 19th century, William Coley, a surgeon at Memorial Hospital in the United States, observed that some cancer patients who were infected with bacteria showed better results. He injected a bacterial toxin into cancer patients and found that it helped prevent the cancer from returning after surgery. This “Coley poison” was used until the mid-20th century, eventually giving way to treatments such as chemotherapy and radiation. Although the work of Dr. Coley did not like it, it laid the foundation for modern immunotherapy, which has been very successful in selected patients.
A groundbreaking study published in New England Journal of Medicine in 2022 by Cersek et al. show this potential. In the study, carefully selected rectal cancer patients achieved complete remission—without surgery—using an immune checkpoint inhibitor. These are agents that remove checkpoints or brakes on T cells that prevent them from recognizing cancer cells. Once T cells can identify cancer cells, they destroy them.
The key to the success of immune checkpoint inhibitors in rectal cancer lies in the specific characteristics of the patient’s tumor. The patient had localized mismatch repair-deficient (dMMR) rectal cancer, a condition in which the tumor’s DNA repair mechanism is defective. This defect causes the accumulation of many DNA errors or mutations, which lead to the production of abnormal proteins that are easily recognized by the immune system. This fundamental defect makes the tumor susceptible to immunotherapy.
Use of CAR-T
Another form of immunotherapy is using CAR-T where the patient’s T cells are reprogrammed in the laboratory and put back into the body to attack the cancer. It is used in certain blood cancers such as leukemia and lymphoma.
Not all cancers respond to immunotherapy, and even when treatment shows initial success, cancer cells can adapt and develop resistance. Factors such as the tumor microenvironment, number of mutations, and PD-L1 expression, play a role in determining the effectiveness of immune checkpoint inhibitors. In addition, attempts to generate non-classical monocytes (I-NCMs) using MDP analog-like chemicals, such as mifamurtide, have shown limited success when tried in actual cancer patients. Complete remission remains elusive. Currently, mifamurtide is only approved as an adjunctive therapy for rare types of bone cancer in children and young adults, which represents a limited scope.
The Northwestern University study highlights the potential of using I-NCM to treat cancer metastases, independent of adaptive components of the immune system such as T cells and B cells. If these findings can be replicated in humans, they could add a new dimension to cancer treatment. While we are still far from a universal cure for cancer, this research provides a glimpse of a future where the body’s own defenses can be used effectively to combat one of humanity’s greatest challenges.
(Dr. Rajeev Jayadevan is Chairman, Research Cell, Kerala State Indian Medical Association)
Published – November 22, 2024 08:00 IST
