Study Explores Immune Evasion Mechanisms in Breast Cancer

To better understand why patients with breast cancer do not respond well to current immunotherapy, a new study evaluated potential ways that the disease avoids immune system detection.

For the study, which was published in PLOS ONE, researchers from Florida State University (FSU) analyzed data from more than 1000 patients with breast cancer, finding that the disease behaves differently than other cancers that are currently treated with immunotherapy. Using the data, the researchers identified 7 clusters of patients based on the immune evasion mechanisms that breast cancer uses to avoid detection.

Current immunotherapy approaches include immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and PD-1/PD-L1. However, the researchers noted that substantial proportions of PD-L1 positive or CTLA4 positive patients do not respond to the corresponding immunotherapies, indicating that these molecules are not reliable biomarkers for response.

“In the era of immunotherapy and personalized medicine, there is an urgent need for advancing the knowledge of immune evasion in different cancer types and identifying reliable biomarkers that guide both therapy selection and patient inclusion in clinical trials,” the researchers wrote in the study.

According to the study, 77.4% of the clustered tumor specimens evade through transforming growth factor-beta (TGF- β) immunosuppression, 57.7% through decoy receptor 3 (DcR3) counterattack, 48% through CTLA4, and 34.3% through programmed cell death. The researchers indicated that targeting TGF-β and DcR3 may provide an especially powerful approach for treating breast cancer because of the proportion of patients who overexpressed these 2 molecules.

Additionally, patients with triple-negative breast cancer (TNBC) clustered equally into 2 subgroups, 1 with impaired antigen presentation and 1 with high leukocyte recruitment, but with 4 different evasion mechanisms. The researchers suggested that this indicated that different patients with TNBC may be treated with different immunotherapy approaches.

Understanding more about breast cancer tumors and their mechanisms can help provide health care professionals with the tools needed to treat patients, as well as help researchers design clinical trials for potential drugs.

“There’s so much data available to understand problems in cancer,” study author Jinfeng Zhang, PhD, associate professor of statistics at FSU, said in a press release about the findings. “Immunotherapy is a big breakthrough, but we still don’t understand why some patients respond and others don’t.”

References

Bou-Dargham MJ, Liu Y, Zhang J, et al. Subgrouping breast cancer patients based on immune evasion mechanisms unravels a high involvement of transforming growth factor-beta and decoy receptor 3. PLOS ONE. 2018. https://doi.org/10.1371/journal.pone.0207799

FSU researchers identify ways breast cancer avoids immune system detection [news release]. FSU’s website. https://news.fsu.edu/news/science-technology/2018/12/18/fsu-researchers-identify-ways-breast-cancer-avoids-immune-system-detection/. Accessed December 18, 2018.