The immune system is supposed to protect us against cancer, but sometimes cancers can hijack parts of the immune system in order to hide from immune attack and spread to other parts of the body.
Breast cancer, if detected early, is among the most successfully treated cancers, with patient survival rates approaching 100 percent for localized tumors. As with most cancers, the chances of complete recovery diminish the further along a cancer has progressed. In breast cancer, overall survival rates can drop as low as 30 percent once the cancer has metastasized (or spread) beyond the primary tumor site to other tissues in the body, such as the lymph nodes, bone, or distant organs.
Most deaths from cancer, in fact, ultimately result from this characteristic ability of cancer to invade other parts of the body and disrupt normal functioning. Researchers, therefore, have invested significant attention on the processes of cancer metastasis in hope of discovering ways to prevent or even reverse this most lethal step in cancer’s progression.
CRI postdoctoral fellow Haihui Lu, Ph.D., at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, is studying some of the unique characteristics that differentiate metastatic cancer cells from primary tumor cells, and specifically aims to understand how these unique characteristics enable breast cancer cells to escape elimination by the immune system.
Under the guidance of a world-renowned cancer biologist, Robert Weinberg, Ph.D., Lu is focusing on how metastatic breast cancer cells interact with a subset of immune cells called macrophages, which normally are capable of engulfing—literally eating—infected, damaged, or cancerous cells. Macrophages are among the first layer of defense when pathogens invade the body, and their rapid response helps to prime our immune system for a secondary, durable immune response that is specifically targeted to the offending pathogens or cancer cells.
Cancer cells acquire the ability to invade and migrate, or metastasize, to other tissues, through a process called Epithelial-Mesenchymal Transition (EMT). Invasive cancers are able to recruit the aid of macrophages, attracting them to the tumor site and then "hijacking" them through processes Lu hopes to elucidate. Having fallen prey to a kind of cellular Stockholm Syndrome, the turncoat macrophages become known as tumor-associated macrophages (TAMs), carrying out the bidding of their cancerous hijackers. Rather than attack the tumor as expected, the errant macrophages shield the tumors from immune system detection and impede the treatment of cancer through immunotherapy. On the other hand, TAMs can also acquire the ability to facilitate the EMT process of cancer cells, rendering them more invasive and resistant to cell death.
The role of TAMs in EMT and resistance to cancer treatment are new fields of study. Dr. Lu is making important contributions to our early understanding of the processes of intercellular communication between tumors and macrophages. Her research may lead to improved diagnostic tools and also facilitate the development of novel cancer therapies that prevent tumor recruitment of macrophages and, as a result, impair a cancer’s ability to metastasize.
Dr. Lu first gained interest in the field of immunology in college during her first class on the subject. At that time, she says, she "found it fascinating that the immune system can actually recognize an enormous, almost unlimited pool of different antigens," which are signature proteins or carbohydrates the immune system recognizes as signals of infectious diseases, damaged cells, or cancer. This inspired her to complete her Ph.D. with a focus on antigen recognition by antibodies.
For Dr. Lu, the most exciting part of her research is "the chance of actually using the immune system to attack tumors and to protect the patient." Despite the complexity of the task she and others in her field face, Dr. Lu is optimistic of tumor immunology’s potential to fight cancer.
"In research, you’re facing these situations where you don’t know what the outcome could be. You could have a hypothesis, but you don’t know what the answer is, and so you have to go a lot of different ways and through a lot of trouble to find out what it really is. Fortunately for me, I like tackling problems and I like these challenges."
It’s fortunate for all of us touched by cancer, too, that Dr. Lu and other CRI-supported researchers have the talent, determination, and patience to work through one of the most important biomedical challenges of our age.
Visit Dr. Weinberg's laboratory website to learn more about Dr. Lu's work.
UPDATE [April 19, 2021]: Dr. Haihai Lu is now an associate director at Novartis Institutes for BioMedical Research (NIBR), leading drug discovery, platform, and strategy development for cancer immunotherapies.
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