自體抗原alpha-烯醇酶在扁平苔藓和口腔鱗狀細胞癌病人中引起的適應性免疫反應

Abstract

口腔扁平苔蘚（OLP）是一種常見的自體免疫性疾病，其表現最主要是位於頰黏膜，舌和牙齦而表徵主要是以多個白色丘疹為標準。之前研究指出，根據估計0.2%口腔扁平苔蘚將發展成口腔鱗狀細胞癌（OSCC）。口腔鱗狀細胞癌 (OSCC) 和口腔扁平苔蘚 (OLP) 都是由口腔角質細胞病變而造成。我們使用這OSCC患者的血漿進行西方墨點法實驗，我們發現口腔癌的細胞裂解物中有高度抗alpha-烯醇化酶的抗體表現。此外我們發現，alpha-烯醇化酶在OLP和OSCC組織切片中有高表現量，並且抗alpha-烯醇化酶的抗體會在在OLP和OSCC患者的血漿中有較高表現。這些結果表示，alpha-烯醇化酶可能是口腔扁平苔蘚和口腔鱗狀細胞癌的發展相關聯的自身抗原中的一個。為了去探測患者周邊血中alpha-烯醇化酶特異性T細胞，我們使用了烯醇化酶多肽池刺激OLP或OSCC患者的CD4和CD8 T細胞。從此實驗中獲得的結果表明，alpha-烯醇化酶特異性T細胞是罕見的，並且多官能反應細胞的功能相較於巨細胞病毒特異性細胞是較為低落。此外我們發現，alpha-烯醇化酶特異性T細胞在腫瘤的百分比都是比周邊血更高。我們的研究結果表明，alpha-烯醇化酶可以是腫瘤相關抗原，並且我們也發現alpha-烯醇化酶特異性T細胞在腫瘤部位尤其豐富。

Oral lichen planus (OLP) is a common autoimmune disorder, which presents as multiple white papules at the buccal mucosa, tongue and gingivae. It’s estimated that 0.2% OLP will develop in to oral squamous cell carcinoma (OSCC). Both OSCC and OLP are lesions of oral keratinocyte. By using OLP and OSCC patients’ plasma to hybridize the oral cancer cell lysate, we found that alpha-enolase was highly expressed in OLP and OSCC tissue sections, and levels of anti-alpha-enolase antibodies were increased in both OLP and OSCC patients’ plasma. These results indicate that alpha-enolase may be one of the self-antigens associated with the development of both OLP and OSCC. To visualize alpha-enolase-specific T cells in the peripheral blood, we used an enolase peptide pool to stimulate OLP or OSCC patient’s CD4 and CD8 T cells. The results obtained from peripheral blood indicate that alpha-enolase-specific T cells are rare and exhibit impaired polyfunctional effector function, as compared to cytomegalovirus-specific cells. In addition, we found that the percentages of alpha-enolase-specific T cells in tumor are higher than in peripheral blood. Our results suggest that alpha-enolase may be a tumor-associated antigen. And alpha-enolase-specific T cells are especially enriched at the tumor site.