Tumor Infiltrating Lymphocytes as a Prognostic and Predictive Biomarker in Breast Cancer

Abstract

Tumor infiltrating lymphocytes (TILs) have been recognized in various cancers and may reflect a host immune response to malignant cells. TILs are a heterogeneous population of various types of mononuclear cells, including CD8 or CD4 + T cells and their subsets, B cells, myeloid derived suppressor cells (MDSC), macrophages, and other cells. Immunosuppressive factors in the tumor microenvironment (TME) that inhibit recruitment and function of TILs include immunosuppressive cells, cytokines secreted by tumor or mesenchymal cells, and co-inhibitory ligands expressed by tumor cells. Despite this complex interplay of immune cells and the TME, higher TIL density is associated with favorable prognosis in certain breast cancer subtypes, including HER2 overexpressing cancers, and “triple negative” cancers that do not express the estrogen and progesterone receptors or overexpress HER2. TILs infiltrating the tumor stroma (sTILs) are associated with higher rates of complete pathologic response to neoadjuvant chemotherapy, decreased recurrence and improved survival in early stage triple negative and HER2-positive breast cancer treated with adjuvant systemic therapy. An international working group has published guidelines on reporting TILs in pathology specimens. In this chapter we review the composition of TILs, mechanisms of immune evasion, recommendations for TILs measurement, and data supporting use of TILs as a prognostic and predictive biomarker in breast cancer.