Exploring The Contribution of Innate Immune Cells to Breast Cancer Immunotherapy

TL;DR

This study investigates how innate immune cells like macrophages and Natural Killer cells contribute to better responses in triple-negative breast cancer immunotherapy, especially in patients with low PD-L1 scores.

Contribution

It reveals that increased infiltration of innate immune cells correlates with improved survival, suggesting an alternative immune response mechanism in TNBC treatment.

Findings

Innate immune cell infiltration is higher in Elite Responders.

Innate and adaptive immune system crosstalk may enhance therapy response.

Innate immune response could be a biomarker for immunotherapy success.

Abstract

Breast cancer is the leading type of cancer in women. About 10-15% of breast cancers are triple-negative breast cancer (TNBC), a subtype with the worst prognosis. Due to the lack of estrogen, progesterone and HER2 receptor expression, chemotherapies have been the standard of care for decades. Immunotherapy has emerged as promising for TNBC treatment. In 2020, the Food and Drug Administration (FDA) granted approval to pembrolizumab in combination with chemotherapy for patients with advanced triple-negative breast cancer. However, only a subgroup of advanced TNBC patients live longer whose tumors have a PD-L1 Combined Positive Score of at least 10 (CPS>=10). There is still an unmet medical need to provide alternative treatment for the rest of patients. Interestingly, a few of patients at UCSD Moores Cancer Center were found to have had excellent responses to pembrolizumab despite low CPS scores (termed Elite Responders). The hypothesis of this project is that there may be an alternative immune response mechanism and/or crosstalk happening between the innate and adaptive immune systems, especially in Natural Killer Cells and Macrophages, that contributed to this unexpected excellent response. Our procedure used ACDBio RNAscope Multiplex Fluorescence v2 method to spatially analyze innate immune cells (Natural Killer cells and macrophages) and adaptive immune cells (T-cells) in the Tumor Micro Environment. Our data demonstrated increased tumor infiltration of innate immune cells (macrophage and Natural Killer cells) in the Elite Responders. This conclusion indicated the joint effort of two immune systems (innate and adaptive) which eventually led to increased survival.