Research Spotlight: Identifying Potential New Protein Targets for Melanoma Therapeutics
Yu-Hwa Huang, PhD and Charles Yoon, MD, of the Department of Medicine and Department of Surgery at Brigham and Women’s Hospital respectively, are co-lead authors of a paper published in Communications Medicine, “High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.”
How would you summarize your study for a lay audience?
Charles Yoon
Yu-Hwa Huang
Some proteins, such as programmed cell death protein 1 (PD1), can stop the immune system from attacking cancer cells and, therefore, support the growth of cancer. Therapies targeting these proteins can be highly effective, but tumors can become resistant.
We applied a method to detect proteins on a single–cell level to uncover human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) patterns in melanoma. We found that increased CEACAM1 expression levels on multiple different immune cell types was associated with tumors resistant to cancer therapy. This points us to a new potential target for therapy for patients with melanoma resistant to treatment.
What knowledge gaps does your study help to fill?
It is important for researchers to identify factors involved in anti-tumor resistance to develop effective cancer therapies. Previous research has revealed that CEACAM1 inhibits an immune response and its levels have been associated with poor patient outcomes.
How did you conduct your study and what did you find?
By using mass cytometry, we created and used a human CEACAM1-specific antibody to provide global insights into the potential cellular basis for CEACAM1’s immune role in melanoma, its association with the state of treatment and its expression relative to PD1 and PD-L1. We discovered that CEACAM1 is found on specific groups of immune cells (including subsets of B cells, monocytic cells, dendritic cells and T cells) in the tumor microenvironment and its presence is associated with treatment-resistant cancer.
What are the implications?
We now understand how CEACAM1 is connected to the immune system’s response to melanoma and how it compares to other proteins involved in immune regulation. Our work highlights CEACAM1 as a potential therapeutic target for melanoma patients whose tumors are resistant to other therapies, such as immune checkpoint inhibitors.
What are the next steps?
We are eager to understand the immune cell-type specific mechanisms by which CEACAM1 operates in the tumor microenvironment.
Authorship: In addition to Huang and Yoon, additional Brigham and Women’s Hospital authors include Amit Gandhi, Thomas Hanley, Yasuyuki Kondo, Xi Lin, Walter Kim, Chao Yang, Duane R. Wesemann and Richard S. Blumberg
Funding: This work was supported by funding from The High-Pointe and Clark Family Foundation, The AFB Fund, Laboratory of Mucosal Immunology Fund and the National Institutes of Health (R01DK051362)
Paper cited: Huang, Y-H, Yoon, CH et al. “High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.” Nature Communication Medicine DOI: https://doi.org/10.1038/s43856-024-00525-8