Clinical significance of tumor-infiltrating lymphocytes in breast cancer

Review Articles
Journal for ImmunoTherapy of Cancer
Sasha E Stanton and Mary L Disis
Description / Abstract: 

Tumor infiltrating lymphocytes (TIL) play an essential role in mediating response to
chemotherapy and improving clinical outcomes in all subtypes of breast cancer. Triple
negative breast cancers (TN) are most likely to have tumors with >50% lymphocytic
infiltrate, termed lymphocyte predominant breast cancer, and derive the greatest
survival benefit from each 10% increase in TIL. The majority of HER2+ breast cancers
have similar level of immune infiltrate as TN breast cancer yet the presence of TILs has
not shown the same survival benefit. For HER2+ breast cancers, type 1 T-cells, either
increased TBET+ tumor infiltration or increased type 1 HER2-specific CD4+ T-cells in
the peripheral blood, are associated with better outcomes. Hormone receptor positive
HER2 negative tumors tend to have the least immune infiltrate yet are the only breast
cancer subtype to show worse prognosis with increased FOXP3 regulatory T-cell
infiltrate. Notably, all breast cancer subtypes have tumors with low, intermediate, or
high TIL infiltrate. Tumors with high TILs may also have increased PD-L1 expression
which might be the reason that TN breast cancer seems to demonstrate the most
robust clinical response to immune checkpoint inhibitor therapy but further investigation
is needed. Tumors with intermediate or low levels of pre-treatment immune infiltrate,
on the other hand, may benefit from an intervention that may increase TIL, particularly
type 1 T-cells. Examples of these interventions include specific types of cytotoxic
chemotherapy, radiation, or vaccine therapy. Therefore, the systematic evaluation of
TIL and specific populations of TIL may be able to both