Scientific Article for Students

Introduction Do you know what cancer is? There are many kinds, like skin, lung, and breast cancer. All cancers start when cells divide and grow uncontrollably, forming lumps called tumors. Tumor cells can travel through the bloodstream to other parts of the body (Figure 1). This process is called metastasis. Breast cancer is the most common cancer in women. Most deaths from breast cancer are due to metastasis. Breast cancer cells can move to the lungs, but they sometimes don’t do much there. These are called dormant cells. This means they don’t divide or grow. They are “asleep”. But these dormant cells can “wake up” and start forming new tumors. This can even happen many years after a cancer survivor has been treated and is in remission. Unfortunately, we don’t know much about why these cancer cells wake up. We got a hint early in the COVID-19 pandemic. We noticed more people with cancer died than we expected. We hypothesized that viruses like influenza (the flu) or the coronavirus SARS-CoV-2 might be waking up these dormant cells. But how? These viruses cause inflammation in the lungs and can trigger the immune system. One key player in inflammation is the protein IL-6. IL-6 tells the body there is a problem and recruits other cells to help. These cells include another key player: helper T cells. They help coordinate the immune response and fight off infections. We thought these key players might be involved in “waking up” the cancer cells. So we designed a series of experiments to find out. Methods Mouse Experiments: We used mice with dormant breast cancer cells in their lungs. We infected these mice by placing tiny droplets of the flu or the coronavirus SARS-CoV-2 into their noses. We collected lung tissue samples from the mice at 3, 6, 9, 15, 28, and 60 days after infection. We stained thin slices of the lungs with colorful dyes that highlight cancer cells. We also used a cell-sorting machine to count the number of cancer cells in the lungs. We used mice that did not produce IL-6. Again, we infected these mice with the influenza virus or coronavirus and studied the lungs at 3, 6, 9, 15, and 28 days after infection. We compared the results to mice that did have IL-6. We repeated the comparison in the second experiment between mice that had fewer helper T cells and those with a normal number. Human Data: We analyzed two large datasets of cancer survivors. One dataset was from the UK, with over 13,000 cancer survivors. The other dataset was from the US, with data from about 36,000 breast cancer patients. For the UK data, we looked at how many people tested positive and negative for COVID-19. For the US data, we compared women with breast cancer who either did or did not get diagnosed with COVID-19. Then we looked at how many died from cancer afterwards or showed cancer growth in the lungs. We used statistics to figure out if testing positive for COVID-19 increased the risk of dying from cancer. Results Mouse Experiments Dormant breast cancer cells grew quickly in the mice after infection. The number of cells increased 100 to 1,000 times within 15 days! (Figure 2) Mice without dormant cancer cells showed no change. Mice without IL-6 had fewer active cancer cells than mice with IL-6. This tells us that IL-6 triggers the dormant cells to divide. Mice with reduced helper T cells also had less cancer cell growth in the following days. This tells us that the helper T cells likely prevent the body from fighting back against the cancer. Human Data: We found that cancer survivors who got COVID-19 were almost twice as likely to die from cancer in the future as those who didn’t. Breast cancer survivors who caught COVID-19 were 44% more likely to develop metastasis in their lungs (Figure 3). The risk of dying from cancer was greatest in the first few months after testing positive for COVID-19. Discussion We found that lung infections like the flu or COVID-19 can make dormant cancer cells wake up and spread. At first, the flu and breast cancer might seem unrelated. The flu affects the lungs, and breast cancer starts in the breast. But we found that they can be connected. A lung infection can sometimes cause cancer cells in the lungs to grow again. The cancer can also prevent an effective immune response against itself. This may help explain why more people with cancer died during the COVID-19 pandemic. It also tells us that infections like the flu or coronavirus can be risky for cancer survivors. There’s good news, though. We now know that IL-6 and helper T cells impact the behavior of dormant cells. Scientists can now design medicines to block these signals. Scientists have developed a drug that lowers IL-6. This would prevent the dormant cells from waking up and dividing. But more research is needed to see if cancer survivors can take this safely. Conclusion For most people, viruses like the flu or COVID-19 cause only mild illness. But for cancer survivors, these infections can be more serious. Since we can’t always tell who has had cancer, it’s important to protect everyone by following simple health rules. This includes washing your hands, covering your mouth when you cough, and staying home when you’re sick. You can also stay up to date on your vaccinations. This gives everyone a better chance to stay healthy.