Abstract
Breast and prostate cancer are the leading causes of death in females and males, respectively. Triple negative breast cancer (TNBC) does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2, resulting in limited treatment options. Androgen deprivation therapy is the standard care for prostate cancer patients; however, metastasis and recurrence are seen in androgen-independent prostate cancer. Both prostate and breast cancer show higher resistance after recurrence and metastasis, which increases the difficulty of treatment. Natural killer (NK) cells play a critical role during innate immunity and tumor recognition and elimination. NK cell function is determined by a delicate balance of inhibitory signals and activation signals received through cell surface receptors. Lectin-like transcript 1 (LLT1, CLEC2D, OCIL) is a ligand of NK cell inhibitory receptor NKRP1A (CD161). Several studies have that reported higher expression of LLT1 is associated with the development of various tumors. Our studies revealed that TNBC and prostate cancer cells express higher levels of LLT1. In the presence of a monoclonal antibody against LLT1, NK cell-mediated killing of TNBC and prostate cancer cells were greatly enhanced. This review highlights the potential that using monoclonal antibodies to block LLT1 - NKRP1A interactions could be an effective immunotherapeutic approach to treat triple negative breast cancer and prostate cancer.
Highlights
Breast cancer is one of the most serious diseases influencing the health of women, whereas prostate cancer threatens the health of men[1]
Lectin-like transcript 1 (LLT1) is a natural killer (NK) cell inhibitory ligand that has been described to contribute to the immunosuppressive properties of glioblastoma, prostate cancer, and triple negative breast cancer[6,7,8,9]
Increased expression of LLT1 was observed after Toll-like receptor induced activation of B cells and dendritic cells, which led to NK cell inhibition via LLT1 - NKRP1A interaction[49]
Summary
Breast cancer is one of the most serious diseases influencing the health of women, whereas prostate cancer threatens the health of men[1]. This review explores LLT1 as a potential immunotherapeutic target for breast and prostate cancer elimination by NK cells. Our lab has found overexpression of LLT1 ligand on TNBC and prostate cancer, which interacts with the NK receptor NKRP1A (CD161) and inhibits NK cell cytotoxicity[9,41]. Blocking inhibitory signals to NK cells using monoclonal antibodies to LLT1 could enhance the lysis of prostate cancer and TNBC cells by NK cells[9,41].
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