CLINICAL SIGNIFICANCE OF TUMOR-INFILTRATING LYMPHOCYTES IN BREAST CANCER
Keywords:
breast cancer, tumor infiltrating lymphocytes, CD8 T cells, FOXP3Abstract
Tumor infiltrating lymphocytes (TILs) play an important role in mediating response to chemotherapy and improving clinical outcomes in all breast cancer subtypes. Triple-negative breast cancer (TN) most likely has tumors with >50% lymphocytic infiltration, termed lymphocyte-dominated breast cancer, and gains the greatest survival advantage for each 10% increase in TIL. Most HER2+ breast cancers have the same level of immune infiltrate as TN breast cancer, but the presence of TIL has not shown the same survival benefit. For breast cancer, HER2+ type 1 T cells, either increased TBET+ tumor infiltration or increased numbers of HER2-specific CD4+ type 1 T cells in peripheral blood are associated with better outcomes. Hormonal receptor-positive HER2-negative tumors tend to have the least immune infiltrate, but are the only subtype of breast cancer that has a poorer prognosis with an increased infiltrate of FOXP3 regulatory T cells. Notably, all breast cancer subtypes have tumors with low, moderate, or high TIL infiltrate. High TIL tumors may also have overexpression of PD-L1, which may be why TN breast cancer appears to show the strongest clinical response to immune checkpoint inhibitor therapy, but further research is needed. On the other hand, tumors with moderate or low levels of immune infiltrate prior to treatment may benefit from an intervention that can increase TIL, especially type 1 T cells. Examples of such interventions include certain types of cytotoxic chemotherapy, radiation therapy, or vaccine therapy. Thus, a systematic assessment of TILs and specific TIL populations can help both in determining prognosis and appropriate sequencing of breast cancer treatment.
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