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Lymph nodes are one of the body鈥檚 first lines of defense against disease. Immune cells are dispatched from these biological police stations to fight off intruders. But somehow, lymph nodes are also the first stop for most metastatic cancers.

鈥淚t鈥檚 paradoxical,鈥� Laboratory(麻豆传媒社区) Assistant Professor Semir Beyaz says. 鈥淭丑别 cancer goes right in, but the immune cells aren鈥檛 doing anything. It鈥檚 important to understand what鈥檚 going on because this is how cancer takes the whole body hostage.鈥�

Beyaz joined with collaborators from Massachusetts General Hospital to investigate. They found that breast cancer cells trick the immune system with help from a molecule called MHC-II. Future therapeutics targeting this molecule may help slow the cancer鈥檚 spread and improve patient outcomes.

鈥淢HC-II acts like breast cancer鈥檚 passport,鈥� Beyaz says. 鈥淚t convinces the lymph node to let the cancer in and protect it. From there, it鈥檚 mayhem.”

In other places, like the intestine, MHC-II helps destroy abnormal cells before they become a problem. But breast cancer鈥檚 version of MHC-II doesn鈥檛 carry the red flags immune cells recognize. So, the lymph node treats it like a false alarm. Beyaz explains:

“Cancer hijacks the lymph node鈥攖he police station. The detectives just say, ‘Welcome. Here’s a comfy couch. Here’s a coffee.’ Cancer bribes the neighboring cells. Then it grows. This is what MHC-II is doing in lymph node metastasis.”

The team found that, in mice, higher levels of MHC-II on a subset of cancer cells led to greater immune suppression in lymph nodes. This caused worse metastasis and shorter survival. When they switched off MHC-II production in cancer cells, lymph nodes awoke to the threat. As a result, the cancer couldn鈥檛 spread as fast, and the mice lived longer.

鈥淚f you get rid of MHC-II in cancer cells, you curb the invasion,鈥� Beyaz explains. 鈥淭丑别 lymph nodes stop suppressing immune response and reduce cancer鈥檚 colonizing abilities.鈥�

Beyaz now hopes to reveal exactly how cancer adapts and spreads. Understanding these mechanisms could bring us closer to new metastasis-blocking therapeutics. But, he cautions, the effectiveness of any potential drug will depend on where cancer first develops.

鈥淔or example, in the gut, we see the opposite of what鈥檚 happening in breast cancer,鈥� Beyaz explains. 鈥淭丑别re are context-specific rules, and this tells us there is no one cure-all.鈥�

Over 300,000 people in the U.S. will be diagnosed with breast cancer this year alone. While a long journey lies ahead, Beyaz thinks this research may someday have clinical implications that lead to better therapies and improve patients鈥� lives.

Written by: Nick Wurm, Communications Specialist | wurm@cshl.edu | 516-367-5940

Funding

National Institutes of Health, Rullo Family MGH Research Scholar Award, Oliver S. and Jennie R. Donaldson Charitable Trust, G. Harold and Leila Y. Mathers Charitable Foundation, The Mark Foundation for Cancer Research, Chan Zuckerberg Initiative, Silicon Valley Community Foundation, STARR Cancer Consortium, Laboratoryand Northwell Health Affiliation, New York Genome Center Polyethnic-1000 Initiative, Deutsche Forschungsgemeinschaft Walter Benjamin Programme, Agency for Science, Technology and Research (A*STAR)

Citation

Lei, P. and聽 Pereira, E.R., et al., 鈥淐ancer cell plasticity and MHC-II-mediated immune tolerance promote breast cancer metastasis to lymph node鈥�, Journal of Experimental Medicine, June 21, 2023. DOI:

Core Facilites

鈥淭丑别 Flow Cytometry Shared Resource offers researchers equipment, training, and assistance with cellular analysis for a variety of applications as well as cell sorting. Our staff oversees equipment maintenance and quality control, trains new users on instrument operation, and assists with assay development and data analysis. We also provide tissue culture facilities for sample preparation and cell maintenance during ongoing flow cytometry experiments.鈥� 鈥� Director Pamela Moody