Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer

Abstract

Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction-sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.

Loss of Fas expression and high expression of HLA-E promoting the immune escape of early colorectal cancer cells

“…Bossard et al (12) revealed that the HLA-E expressed in colorectal cancer cells may combine with the HLA-E receptor CD94/NKG2A expressed on the surface of CTL and NK cells, which contributed to the inhibition of the activity of the CTL and NK cells. Zhen et al (21) hypothesized that the overexpression of HLA-E in colorectal cancer cells was often associated with lower long-term disease-free survival rate and poor prognosis. Levy et al (13) demonstrated that HLA-E expression on the surface of colorectal cancer cell membranes could inhibit the cetuximab-mediated antibody-dependent cell-mediated cytotoxicity, which may promote the immune evasion of colorectal cancer cells.…”

HLA-E expression and its clinical relevance in human renal cell carcinoma

“…in laryngeal carcinoma [14], mammary carcinoma [15], small cell lung cancer [16], pancreatic cancer [17] ovarian carcinoma [11] and in colorectal carcinoma [18, 19]. Concerning hematopoietic malignancies HLA-E surface expression was found in a high percentage of lymphoid tumor cells and was associated with a protection from NK cell-mediated cytotoxicity [20].…”

Involvement of IL-10 and TGF-β in HLA-E-mediated neuroblastoma migration and invasion

“…The anti-HLA-E monoclonal antibody 3H2679 (Santa Cruz, USA) was used. HLA-E expression was evaluated as described previously [5]. …”

“…In the major mechanism underlying tumor immune escape, HLA-E binds to the leading peptides of HLA-A, -B, -C, and -G, activating the CD94/NKG2A receptor and delivering an inhibitory signal to NK and CTL cells [3]. Studies have found that HLA-E is highly expressed in a variety of tumors [4] and closely associated with certain biological characteristics of tumors [5]. However, HLA-E expression in NB tissue and its clinical significance is yet to be determined.…”