  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.
