New research from Memorial Sloan Kettering Cancer Center (MSK) sheds new light on how the gut protects itself by sensing gut bacteria; finds a subtype of glioma-associated macrophages that appear to play a pivotal role in progression; and demonstrates that reduced surgery is an option for some thyroid cancer patients.
MSK researchers shed new light on how the gut protects itself by sensing gut bacteria
In the human gut, a single layer of epithelial cells separates waste and microbes from underlying tissues. Immune cells such as macrophages are key players in repairing that barrier, resolving inflammation, and preventing harmful bacteria from infiltrating the body.
New research from MSK’s Sloan Kettering Institute reveals that gut epithelial cells do more than just block microbes — they actively sense bacteria and use that information to rally protective immune cells.
A research team from the lab of senior study author Gretchen Diehl, PhD, led by research scholar Ming-Ting Tsai, PhD, showed that the sensing of bacterial flagella (a whiplike appendage that cells use to move around) by intestinal epithelial cells triggers the recruitment of macrophages to the tissue, where they provide barrier support.
In a series of experiments using human organoids and mouse models, the researchers found that intestinal epithelial stem cells express TLR5, the receptor for flagellin. Flagellin binding to epithelial TLR5 activates the secretion of molecules to recruit macrophages, offering protection in colitis models. Meanwhile, the loss of flagellin or the inability to detect it results in increased colitis susceptibility.
Overall, the study suggests this epithelial sensing might be harnessed to bolster immunity and that additional microbial cues driving immune responses in the gut remain to be discovered. Read more in Science Immunology.
Subtype of glioma-associated macrophages appear to play a pivotal role in progression
The immune environment in tumors is a key roadblock that can prevent immunotherapies from being effective. This is particularly true of brain cancers such as gliomas, which — because they are located in the brain — are largely protected from the immune system. But brain tumors do contain immune cells called macrophages, and researchers have long suspected that these glioma-associated macrophages (GAMs) support the tumor in some way.
In a new study led by MSK neurosurgeon-scientists Kenny Kwok Hei Yu, MBBS, PhD, and Viviane Tabar, MD, researchers took a closer look at the immune cells contained within gliomas. Using single-cell analysis to characterize the subtypes of GAMs in a group of glioma patients, they identified a subpopulation they named malignancy-associated GAMs (mGAMs) that appear to play a key role in the growth and spread of these tumors. These mGAMs contain molecular characteristics that suggest they help to promote tumor growth, and they appear to be enriched within the areas of gliomas that are more aggressive.
“These mGAMs appear to play a pivotal role in the progression of glioma and are a potential therapeutic target for glioma treatments,” Dr. Yu says. “This discovery paves the way for developing a targeted therapy that could block this subpopulation, allowing other types of immunotherapy to be more effective.” Read more in Cancer Cell.
Reduced surgery an option for some thyroid cancer patients
A new study led by MSK head and neck surgeon Ian Ganly, MD, PhD, found that some people with thyroid cancer may not need to have the entire thyroid gland removed. Instead, removing just half of the gland (thyroid lobectomy) was just as effective while reducing the risk of surgical complications and side effects.
Standard treatment for people whose papillary thyroid cancer had spread to nearby lymph nodes in the neck has been to remove the entire thyroid plus the surrounding nodes (total thyroidectomy), followed by treatment with radioactive iodine. This extensive surgery usually means the patient must take lifelong hormone replacement and carries the risk of causing low blood calcium — as well as temporary or permanent voice changes.
Dr. Ganly and colleagues looked at results from 37 MSK patients who had received a thyroid lobectomy and compared them with 37 patients who had received a total thyroidectomy plus radioactive iodine treatment. They found no significant difference between the groups in disease recurrence or survival.
“These results suggest that carefully selected thyroid cancer patients can benefit from less extensive surgery,” Dr. Ganly says. “This is part of an encouraging trend in thyroid cancer care, which looks to minimize treatment when the disease is considered low risk.”
Read more in JAMA Otolaryngology—Head & Neck Surgery.