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Tumor Microenvironment

Calvi & WilliamsThe powerful impact of the microenvironment has been under the spotlight nationally in recent years and it’s been a longtime research pillar at Wilmot, particularly for blood cancers such leukemia and lymphoma. We’ve discovered that the microenvironment can play either a positive or negative role in the way cancer behaves. Ultimately, our goal is to find ways to target the microenvironment with treatments that could boost the effectiveness of other types of cancer therapies. Our Tumor Microenvironment research program also has a strong immune system component because immune cells are constantly on patrol for cancer and play a significant role in aging.

Some areas of special interest:

  • The bone marrow. The crosstalk that occurs among the non-blood cells in the bone marrow microenvironment is believed to be a mechanism that fuels cancer. We not only investigate the cell signals and interactions in the bone marrow microenvironment that promote malignancy, but also marrow failure and how to disrupt the microenvironment and affect the disease process. The bone marrow is crucial to aging because it is the site of healthy blood production.
  • Myelodysplastic Syndromes or MDS. This is a pre-leukemia condition stemming from bone marrow failure that occurs in older adults. Wilmot has a long history of expertise in MDS thanks to professor emeritus John Bennett, M.D., who defined the disease and founded The Myelodyplastic Syndromes Foundation. Building on Bennett’s work, our team is investigating how the bone marrow microenvironment causes or contributes to the development of MDS and whether the microenvironment could be a new point of intervention.  
  • Macrophages. These cells, which are innate to the blood and immune system, act to fight infection. Macrophages also gobble up all dying cells in the immune system. However, when their normal function goes awry the macrophage’s good-guy role switches to that of a villain: macrophages can also provide growth factors for tumor cells and block the immune system from doing its job to kill early cancers. Our team studies the behavior of macrophages for evidence that these cells are also involved in treatment resistance.  
  • The immune system’s role in cancer is a key to survival. Immunotherapy, which stimulates a patient’s own immune system to fight malignancy, is one of the biggest clinical breakthroughs in recent years. One of our special interests is in pancreatic cancer research, to discover how the tumor microenvironment protects cancer cells from being destroyed, and how to manipulate this occurrence with new drugs.
  • Barriers to immunotherapy. Two main challenges of this treatment are: overstimulation of the immune system that causes life-threatening side effects in patients, and cancer’s ability to hide from killer immune cells. One of our scientists is using a process called optogenetics to demonstrate that non-toxic LED light can guide cancer-fighting T-cells directly toward tumors.
  • Radiation therapy side effects. Although radiation treatment is widely used and absolutely necessary in many cases, and the field of physics has refined the way treatment is delivered to tumors—DNA damage still occurs to nearby healthy tissues. Because of this, short-term and long-term side effects continue to harm cancer survivors. Our team takes a unique approach by studying how to minimize damage to the normal cells and tissues surrounding the tumor. We use advanced technology to investigate the imbalances in the microenvironment in response to radiation treatment, and whether stabilizing the healthy tissue might also prevent cancer from recurring near the treatment site.