Novel immune targets for the treatment of triple-negative breast cancer

To overcome mechanisms of primary and secondary resistance to the anti-tumor immune response, novel targets such as ICOS, LAG3, and TIM3 are currently being explored at preclinical and early-phase clinical levels.

This article examines the landscape of the immune therapeutics investigated in early-phase clinical trials for TNBC. Preclinical rationale is provided for each immune target, predominant expression, and function. Clinical implications and preliminary available trial results are discussed and finally, we reflect on aspects of future expectations and challenges in this field.

Several immune strategies have been investigated in TNBC, including co-inhibitory molecules beyond PD1-PD-L1 axis, co-stimulatory checkpoints, cancer vaccines, adoptive cell transfer, combination therapies, as well as different routes of administration. Most of approaches showed signs of anti-cancer activity and a good safety profile in early-phase clinical trials. Since IO provided benefit only to a small subgroup of TNBC patients so far, identifying predictive biomarkers is a priority to refine patient-selection. Data from ongoing clinical trials, with the gradually improving interpretation of the breast tumor immune environment, will hopefully refine the role of new immune targets for the treatment of TNBC.