Breast and Ovarian Carcinoma Overexpress HLA-G, a Neglected Cancer Immunosuppressive Protein ()
ABSTRACT
Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an
important role in protection of fetal cells from maternal NK lysis. HLA-G also
mediates tumor escape, but the immunosuppressive role is often neglected. These
studies have focused on the examination of HLA-G expression in human breast and
ovarian carcinoma and HLA-G immunosuppressive role in NK cytolysis. Methods: We examined HLA-G
expression in breast and ovarian carcinoma cell lines by real time PCR, ELISA
and immunofluorescent staining, and in frozen breast and ovarian carcinoma
tissues by immunohistochemistry (IHC). We treated the breast cancer cell lines
with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured
by using MTT assay. Results: We find breast and ovarian cancer cell lines increase the expression of
HLA-G mRNA and protein, compared to normal cells. IHC shows that 100% of frozen
breast and ovarian carcinoma tissues overexpress HLA-G protein. HLA-G IHC
scores of breast and ovarian carcinoma are significantly higher than normal
breast and ovarian tissues, respectively (both p < 0.01). Blocking HLA-G of
the breast cancer cells by the antibody increases NK cytolysis. Progesterone
upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased
HLA-G expression by progesterone suppresses the NK cytolysis. Conclusion: Human breast and
ovarian carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G
protein by antibody improves the cytolysis of NK cells against human breast cancer
cell lines. In contrast, upregulation of HLA-G expression by progesterone
impairs NK cytolytic function. Thus, HLA-G is a new immune checkpoint protein
and potential cancer immunotherapeutic target.
Share and Cite:
Jiang, X. , Baucom, C. , Jiang, T. and Elliott, R. (2022) Breast and Ovarian Carcinoma Overexpress HLA-G, a Neglected Cancer Immunosuppressive Protein.
Advances in Breast Cancer Research,
11, 153-172. doi:
10.4236/abcr.2022.113013.
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