Abstract
Prostate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors. Previously, we identified Lectin-like transcript-1 (LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A inhibits NK cell activation. In this study, we have found that LLT1 was overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in primary prostate cancer tissues both at the mRNA and protein level. We further showed that LLT1 is retained intracellularly in normal prostate cells with minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of prostate cancer cells. The results indicate that prostate cancer cells may evade immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and therefore may be a new therapeutic option for treatment of prostate cancer.
Highlights
Prostate cancer (PC) is the most frequently diagnosed cancer and the second leading cause of cancer-related death in American men [1]
The results indicate that prostate cancer cells may evade immune attack by Natural Killer (NK) cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction
We suggest that blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and may be a new therapeutic option for treatment of prostate cancer
Summary
Prostate cancer (PC) is the most frequently diagnosed cancer and the second leading cause of cancer-related death in American men [1]. The majority of patients are treated successfully with radical prostatectomy or radiation therapy, approximately 30– 40% of patients will develop recurrent disease [2]. Of the many treatment approaches for recurrent prostate cancer that no longer responds to hormonal agents, the emergence of immunotherapy such as immune checkpoint inhibitors and therapeutic cancer vaccines has revolutionized cancer treatment [4]. Prostate cancer is an excellent tumor target for immune-based therapies as it has an indolent disease course, which allows the immune system to generate an immune response. Prostate specific antigen (PSA) allows for detection of disease when the cancer is at the micrometastatic level, allowing for small volumes of disease to be treated
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