Study sheds light on how breast cancer cells evade immune surveillance and survive in lymph nodes

BOSTON– In breast cancer, nearby lymph nodes, which are part of the immune system, are usually the first place where cancer spreads, and from here cancer cells can travel to other parts of the body, such as the brain, lungs, liver, and bones.

New research led by Massachusetts General Hospital (MGH) researchers reveals how cancer cells suppress cancer immune responses in the lymph nodes in order to survive and spread or metastasize.

The findings, which have been published in the Journal of Experimental Medicine, could lead to new strategies to prevent this suppression and unleash the immune system to fight cancer.

In a breast cancer mouse model, the scientists analyzed and compared the gene expression patterns of individual cancer cells that were located in breast tissue or had spread to lymph nodes.

They also studied how immune cells reacted in the presence of these cancer cells.

Finally, the team examined published data on gene expression patterns in human breast cancer cells during lymph node metastases.

These efforts revealed that some breast cancer cells in mouse and human lymph nodes show increased expression of genes encoding MHC class II (MHC-II) proteins, which, when present on the cell surface of antigen-presenting cells, are involved in initiating of the immune system. reactions.

However, the MHC-II+ cancer cells lacked so-called costimulatory molecules typically present on antigen-presenting cells that alert immune cells to danger.

As a result, the lymph nodes had more tolerant immune cells and fewer activated immune cells.

Knocking out the gene for MHC-II in cancer cells reduced lymph node metastasis and the expansion of permissive immune cells in mice, leading to longer animal survival.

On the other hand, overexpression of a protein that increases MHC-II expression exacerbated lymph node metastasis and caused over-expansion of permissive immune cells.

“Our findings have important implications for developing effective treatments to target lymph node metastases, prevent cancer spread to other organs, and restore antitumor immunity in the tumor-draining lymph nodes,” said co-lead author Pin-Ji Lei, PhD, a postdoctoral fellow. researcher in radiation oncology at MGH.

Co-senior author Timothy P. Padera, PhD, the 2021-2026 Rullo Family MGH Research Scholar and an associate professor of Radiation Oncology at Harvard Medical School, notes that additional research is needed to fully understand the clinical significance of the group’s findings. to decide.

“We need to see whether the reprogramming of cancer cells by the lymph node microenvironment affects patients’ immune responses to cancer.”

Other co-authors are Ethel R. Pereira, Patrik Andersson, Zohreh Amoozgar, Jan Willem Van Wijnbergen, Meghan J. O’Melia, Hengbo Zhou, Sampurna Chatterjee, William W. Ho, Jessica M. Posada, Ashwin S. Kumar, Satoru Morita, Lutz Menzel, Charlie Chung, Ilgin Ergin, Dennis Jones, Peigen Huang and Semir Beyaz.

This work was supported by grants from the National Institutes of Health; the Rullo Family MGH Research Scholar Award; the Oliver S. and Jennie R. Donaldson Charitable Trust; the Harold and Leila Y. Mathers charitable foundation; Mark Foundation for Cancer Research; the Chan Zuckerberg Initiative/Silicon Valley Community Foundation; the STARR Cancer Consortium; the affiliation of CSHL and Northwell Health; the New York Genome Center’s Polyethnic-1000 initiative; the Walter Benjamin program; the German Research Foundation; the Science, Technology and Research Agency; METAvivor Foundation; the American Association for Cancer Research/Breast Cancer Research Foundation; and the Karin Grunebaum Cancer Research Foundation.

About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s original and largest teaching hospital. The Mass General Research Institute conducts the largest hospital research program in the country, with annual research activities exceeding $1 billion and comprising more than 9,500 researchers working in more than 30 institutes, centers and departments. In July 2022, Mass General was voted #8 in the US news and world report list of “America’s Best Hospitals.” MGH is a founding member of the Mass General Brigham healthcare system.

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