MICA分子在NK细胞杀伤乳腺癌中的作用

Roles of MICA in breast tumor

目的观察乳腺肿瘤细胞膜MHCⅠ链相关分子A(MHC class I chain-related gene A,MICA)及血清中可溶性MICA表达,探讨MICA在NK细胞杀伤乳腺癌中的作用。方法流式细胞术检测膜型MICA(mMICA)及NK细胞表面NKG2D表达,观察膜型MICA、可溶性MICA(sMICA)对NKG2D表达的影响;免疫组织化学检测膜型MICA及可溶性MICA的表达及分布;抗体封闭法观察膜型MICA与NKG2D相互作用。结果乳腺细胞膜型MICA在正常组织不表达,在良性肿瘤表达量为(38.5±7.5)%,恶性肿瘤表达量为(53.2±5.6)%。可溶性MICA含量在健康成年人为阴性,在乳腺良性肿瘤患者血清中含量(76.8±22.3)pg/mL,在恶性肿瘤患者中含量(205.36±71.27)pg/mL。经NKG2D或MICA抗体封闭后,NK细胞的杀瘤活性显著减弱。含可溶性MICA的血清可明显下调NKG2D的表达。结论大部分乳腺肿瘤细胞膜都有MICA的表达,可作为乳腺肿瘤相关性抗原。膜型MICA与NKG2D的相互识别在介导NK细胞抗乳腺癌中起重要作用,而可溶性MICA通过下调NKG2D表达介导肿瘤免疫逃逸。

Objective To value the expression of MHC class Ⅰ chain-related gene A （MICA） on breast tumor cellular membrane and the expression of soluble MICA （sMICA） in serum of patients with breast tumor for investigating the roles MICA in anti-breast cancer. Methods Flow cytometry （FCM） was performed to identify the expression of membrane MICA （mMICA） on breast tumor tissues and cell lines, and the expression of NKG2D on NK cells. The effects of mMICA and sMICA on the expression of NKG2D were observed by FCM. Immunohistochemistry was used to detect the expression and distribution of the sMICA and mMICA on breast tumor tissues. The reactionshipe between MICA and NKG2D was evaluated by purified-antibody blockade. Results mMICA was not detected on normal breast tissues, but （38.5±7.5）% on benign breast tumor or （53.2 ± 5.6）% on malignant breast tumor, sMICA was not detected in the serum of healthy person, but （76.8 ± 22.3） pg/mL in benign breast tumor patients or （205.36 ± 71.27） pg/mL in malignant breast tumor patients. Cytotoxicity of NK cells was decreased because of NKG2D or MICA antibody blockade. The expression of NKG2D was decreased after the NK cells were cultured with sMICA. Conclusion MICA is expressed on lots of breast tumor cellular membrane and would be regarded as tumor associated antigen （TAA）, thus MICA-expressed malignant cells were recognized by NK cells. MICA-NKG2D plays a critical role in tumor immune surveillance via NK cells, sMICA reduces the expression of NKG2D and leads to immune escape of breast tumor.