PD-L1 and PD-1 Mechanism in Triple Negative Breast Cancer Tumors

Introduction/ Background

Triple negative breast cancer (TNBC) is characterized by the absence of estrogen receptor, progesterone receptor and HER 2 amplification. TNBC is a very aggressive and highly metastatic cancer which does not respond to hormone therapies. The tumor microenvironment is the cellular environment in which the tumor exists which contains many components including inflammatory mediators and immune checkpoints.

Methods/ Materials

Not much is known about the mechanism of PD-L1 in TNBC so in this study, we studied the effect of PD-L1 overexpression in co-culture with PD-1 overexpression. Three cell lines were involved: MDA-MB-231, BT 549 and HEK 293 cells. Co-cultures were done in order to look at the proliferation and morphology changes between the cell lines. FACS of both co-cultures was done to look at the transfer of cherry from MDA-MB-231 cells (or BT 549) to HEK 293 cells. MDA-MB-231 was grown with recombinant PD-1 (rPD-1) to compare with the results in the co-cultures.

Results

We grew four combinations for the co-cultures and our results indicate that the combination that has both PD-L1 and PD-1 being overexpressed has higher proliferation and more drastic changes in morphology (such as elongated and clustered cells). FACS test indicated that the HEK 293 cells did indeed take some cherry and became more positive. When we tested rPD-1 on the cell lines with the same combination, we saw the same results in the combination that has both PD-L1 and PD-1 being overexpressed.

Conclusion

The findings of this study indicate that PD-L1 expression in combination with PD-1 is prevalent in breast cancer and does affect both the morphology and the proliferation of the cell lines involved in this study. The initial experiments on the mechanism of PD-L1 with PD-1 is being followed up with subsequent experiments on the effect of this mechanism on triple negative breast cancer tumor progression.