The immune microenvironment in metastatic breast cancer is “more inert” compared with that of primary tumors. This is the conclusion reached by Yale researchers after looking at the levels of tumor infiltrating lymphocytes (TILs), expression of the programmed death-ligand 1 (PD-L1), and 730 immune-related genes in primary and metastatic breast cancer samples.

Because metastatic lesions escape immune surveillance at the primary site, they likely have lower immunogenicity compared to the corresponding primary tumor, the researchers reasoned. The results of their study, published in the Annals of Oncology, support this notion and show a lower level of TILs, a lower expression level of PD-L1, and immune gene signatures that are characteristic of immune suppression in metastatic breast cancer tissue samples compared with primary tumor tissue.

“The most important observation that we made is that metastatic lesions have fewer TILs and show downregulation of chemotactic and immune-activating cytokines, decreased antigen presentation, and overall lower expression of many immuno-oncology drug targets and at the same time we saw upregulation of immunosuppressive molecules,” corresponding author Lajos Pusztai, MD, DPhil, director of breast cancer translational research at the Yale Cancer Center, New Haven, Connecticut, told Cancer Therapy Advisor.

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“This is the first study to examine a comprehensive immune landscape of matching primary tumors and metastasis,” Dr Pusztai said. He explained that earlier studies were both smaller and only tested a limited number of immune parameters such as TILs, or 1 or 2 immune-cell populations, or PD-L1 expression only.2-4 “The reason for lack of studies in this space is the limited number of samples that are available,” he said.

“Our data suggest that breast cancer becomes less immunogenic during metastatic progression, [which] results in an attenuated immune response at the metastatic sites compared to the primary tumor in the breast,” Dr Pusztai said.