Breast cancer is the most common cancer among women worldwide, and while treatments have advanced, aggressive forms like triple-negative breast cancer (TNBC) and certain estrogen receptor-positive (ER+) tumors remain challenging to treat. In a groundbreaking study, MCW researchers have uncovered a way to identify patients who may benefit from immunotherapy, a treatment that has shown promise in other cancers but is still emerging in breast cancer. By examining PD-L1 and PD-L2—two proteins that help the immune system recognize and attack cancer cells—they found that testing tumors for both could more accurately predict which patients are likely to respond to this innovative treatment. Their findings, recently published in the Journal of Personalized Medicine, could help bring more tailored treatments to patients with the hardest-to-treat breast cancers.
“While PD-L1 has been the primary focus in cancer immunotherapy, our findings suggest that PD-L2 could help identify additional patients who might benefit, particularly those with aggressive tumors,” said Julie Jorns, MD, Yunguang Sun, MD, PhD, and Lubna Chaudhary, MD, the study’s lead authors. “PD-L2 binds more strongly to the PD-1 receptor, making it a valuable marker for cancers that are harder to treat. Incorporating PD-L2 testing could expand the number of patients eligible for immunotherapy, offering hope to those who might not respond to standard therapies. If validated in larger studies, this approach could significantly improve breast cancer care and patient outcomes.”
Using the Biorepository and Tissue Analytics Shared Resource, the study team performed immunohistochemistry—a technique used to detect specific proteins in tissue samples—to assess PD-L1 and PD-L2 expression in cancer and immune cells across 23 ER+ and 9 TNBC tumors. Their findings revealed:
- All 9 TNBC tumors were positive for PD-L1, with 89% also positive for PD-L2.
- Among the 23 ER+ tumors, 74% tested positive for PD-L2, but only 39% for PD-L1.
- Of the PD-L1-negative ER+ tumors, 80% still tested positive for PD-L2.
These results suggest that PD-L2 could be a crucial marker for identifying patients who might not qualify for immunotherapy based on PD-L1 testing alone. Building on the team’s earlier study that linked high PD-L2 levels to early recurrence in ER+ breast cancer, these new findings further reinforce the protein’s potential as a key factor in treatment decisions. “Using PD-L2 as an additional marker could expand enrollment in clinical trials for PD-1 inhibitors, offering more patients the opportunity to benefit from these promising treatments and improving outcomes for those who might otherwise be overlooked,” the team said.
During Breast Cancer Awareness Month, the MCW Cancer Center joins the national movement in advocating for cutting-edge research, particularly for underserved communities facing disparities in care. For example, Black women in the U.S. have a 40% higher breast cancer mortality rate than white women, despite similar diagnosis rates. Research like this is helping close the gap by ensuring that people from all backgrounds are considered for innovative treatments that could save their lives.
“The MCW Cancer Center is dedicated to advancing breast cancer research through patient-focused approaches,” the team noted. “To our knowledge, this is the first study to include PD-L2 as an eligibility criterion for immunotherapy, and our findings could significantly impact breast cancer treatment strategies nationwide.”
Looking ahead, the team is excited to expand clinical trials to further explore PD-L2 as a marker for identifying which patients could benefit from immunotherapy. As they near the completion of patient enrollment in their current phase 2 study, led by Dr. Chaudhary, their focus is on understanding how PD-L2 can more accurately predict treatment response and guide personalized therapies for aggressive breast cancers.
Read the full study in the Journal of Personalized Medicine.