Author: Sean Krivitsky, Class of 2026

Breast cancer is the most frequently diagnosed form of cancer in the world and is one of the leading causes of cancer-related deaths. Triple-negative breast cancer (TNBC), a common type of breast cancer, is fast-growing and is associated with consistent poor prognosis. Unlike several other types of breast cancer, TNBC possesses a unique pathogenic mechanism, which means that it cannot be treated through some of the common therapeutic approaches to breast cancer since several key therapeutic targets are missing. This absence has made TNBC particularly difficult to treat, which presents a dire need for the identification of novel therapeutic targets for this specific type of breast cancer. Within the body, various types of immune cells can infiltrate into the tumor microenvironment and influence different characteristics such as their growth rate and metastatic potential. Through advanced single-cell RNA sequencing techniques, Dr. Gatha Thacker, in collaboration with the Dos Santos lab at Cold Spring Harbor laboratory, identified a specific subclass of immune cells called natural killer (NK) cells as playing a key role in TNBC progression.

More specifically, a type of immature NK cells was identified as contributors to tumor progression. These immature NK cells possess a reduced cytotoxic activity compared to terminally differentiated NK cells. These cells were determined to be upregulated in TNBC which challenges more widespread beliefs that NK cells generally contribute to the destruction of cancer cells through processes of anticancer immunity. Notably, in previous TNBC models, depleting NK cell populations at various cancer stages resulted in slowed cancer progression. These specific NK cells that were found to contribute to TNBC tumor progression possessed a variety of characteristics that prevented them from maturing and obtaining enhanced cytotoxic, anti-cancer qualities.

This groundbreaking research is incredibly significant because it points to multiple avenues for improving therapeutic opportunities for the treatment of TNBC. Not only did the depletion of these immature NK cells impact the progression of TNBC in several of the research group’s models, but it was also paired with current cancer therapies aimed at treating several types of cancer such as anti-PDL1 therapy. Ultimately, these experiments revealed that combinations of widely used cancer therapies and the depletion of these immature NK cells improved their efficiency, reducing cancer progression.

Figure 1. Immunofluorescence imaging of invasive breast cancer cells.

Works Cited

[1] Thacker, G., Henry, S., Nandi, A., Debnath, R., Singh, S., Nayak, A., Susnik, B., Boone, M. M., Zhang, Q., Kesmodel, S. B., Gumber, S., Das, G. M., Kambayashi, T., Dos Santos, C. O., & Chakrabarti, R. (2023). Immature natural killer cells promote progression of triple-negative breast cancer. Science Translational Medicine, 15(686). https://doi.org/10.1126/scitranslmed.abl4414 

[2] Image retrieved from: https://commons.wikimedia.org/wiki/File:Invasive_Breast_Cancer_in_3D.jpg