Nicotine treatment regulates PD-L1 and PD-L2 expression via inhibition of Akt pathway in HER2-type breast cancer cells

Abstract

The immune checkpoint molecules such as PD-L1 and PD-L2 have a substantial contribution to cancer immunotherapy including breast cancer. Microarray expression profiling identified several molecular subtypes, namely luminal-type (with a good-prognosis), HER2-type (with an intermediate-prognosis), and triple-negative breast cancer (TNBC)-type (with a poor-prognosis). We found that PD-L1 and PD-L2 mRNA expressions were highly expressed in TNBC-type cell lines (HCC1937, MDA-MB-231), moderately expressed in HER2-type cell line (SK-BR-3), and poorly expressed in luminal-type cell lines (MDA-MB-361, MCF7). The PD-L1 and PD-L2 expression in SK-BR-3 cells, but not those in HCC1937 and MDA-MB-231 cells, decreased by nicotine stimulation in a dose-dependent manner. In addition, nicotine treatment decreased the phosphorylation of Akt in SK-BR-3 cells, but not in other cell lines. These results show that nicotine regulates the expression of immune checkpoint molecules, PD-L1 and PD-L2, via inhibition of Akt phosphorylation. This findings may provide the new therapeutic strategies for the treatment of breast cancer.

Evaluation of PDL1 positive cancer cell‐specific binding activity of recombinant anti‐PDL1 scFv

“…14,15 SK-BR3, MDA-MB-231, and MCF-7 cells were isolated from the mammary gland of a patient which adenocarcinoma, [16][17][18][19][20] and are widely used for breast cancer research. Among these three cell lines, SK-BR3 and MDA-MB-231 overexpress PDL1, [21][22][23][24][25] whereas low levels of cell surface PDL1 are observed in MCF-7. 22,24,25 HEK293T is an immortalized human embryonic kidney cell line with a gene encoding the large T antigen of simian virus 40, 26,27 whose PD-L1 expressing level is not clear.…”

“…Among these three cell lines, SK-BR3 and MDA-MB-231 overexpress PDL1, [21][22][23][24][25] whereas low levels of cell surface PDL1 are observed in MCF-7. 22,24,25 HEK293T is an immortalized human embryonic kidney cell line with a gene encoding the large T antigen of simian virus 40, 26,27 whose PD-L1 expressing level is not clear. In this study, we seeded 5 Â 10 5 cells of each cell line in a mediumcontaining 6-well culture plate with glass coverslips on the bottom and incubated overnight.…”