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| Clinical study of high expression of CD8+T lymphocytes surface inhibitory receptor NKG2A in lung adenocarcinoma tissue |
| MA Mingyang1 YUAN Xiang1 LIU Yiwen1 SUN Jiangtao2 |
1.Clinical Medical College of He′nan University of Science and Technology the First Affiliated Hospital of He′nan University of Science and Technology Cancer Institute of He′nan University of Science and Technology He′nan Key Laboratory of Cancer Epigenetics, He′nan Province, Luoyang 471003, China;
2.Clinical Medical College of He′nan University of Science and Technology the First Affiliated Hospital of He′nan University of Science and Technology, He′nan Province, Luoyang 471003, China |
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Abstract Objective To analyze the correlation between expression of CD8+T cell surface inhibitory receptor NKG2A and clinicopathological characteristics and 5-year survival in patients with lung adenocarcinoma, and to explore its clinical significance and prognostic value. Methods From January 2014 to March 2015, 130 cases of lung adenocarcinoma with epidermal growth factor receptor (EGFR) (+) were resected in the First Affiliated Hospital of He′nan University of Science and Technology, and the paraffin-embedded samples of the carcinema tissues and adjacent lung tissues of patients with lung adenocarcinoma were selected as the research objects, immunohistochemistry was used to detect the expression of NKG2A protein on the surface of infiltrated CD8+T lymphocytes, and the correlation between NKG2A expression and clinicopathological characteristics and 5-year survival in patients with lung adenocarcinoma was analyzed. The influence of each factor on prognosis was analyzed by Cox regression method. The correlation between NKG2A protein expression and survival time was analyzed by Kaplan-Meier method. Results The expression of NKG2A protein was observed in the membrane of infiltrated CD8+T lymphocytes in lung adenocarcinoma and corresponding adjacent lung tissues, in lung adenocarcinoma tissues, the immunohistochemical score of NKG2A was higher than that of high differentiation and low differentiation than that of medium differentiation (P ＜ 0.05). High expression of NKG2A protein was associated with differentiation, lymph node metastasis, clinical stage and 5-year survival in patients with lung adenocarcinoma (P ＜ 0.05). The degree of differentiation, lymph node metastasis, clinical stage and high expression of NKG2A protein were independent risk factors for the prognosis of patients with lung adenocarcinoma. Moreover, the 5-year survival rate and median survival time of patients with high NKG2A protein expression were significantly lower than those with low expression, with statistically significant differences (P ＜ 0.05). Conclusion The high expression of the inhibitory receptor NKG2A on the surface of CD8+T lymphocytes may promote the development of lung adenocarcinoma by weakening its anti-tumor immunity. Inhibition of NKG2A expression may provide a new idea and an effective treatment for lung adenocarcinoma.
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展[3，14-16]。同时肿瘤细胞对免疫细胞抑制性受体表达的调节，是肿瘤削弱宿主微环境中免疫细胞杀伤力、诱导免疫耐受甚至功能耗竭，最终导致肿瘤免疫逃逸的重要机制[17-19]。
本研究显示肺腺癌组织中CD8+T淋巴细胞表面抑制性受体NKG2A蛋白表达显著升高，提示肿瘤组织中可聚集大量不具备杀伤能力的CD8+T淋巴细胞，从而增加肿瘤微环境的免疫抑制状态。且NKG2A蛋白表达随分化程度降低而逐渐升高，提示随着肿瘤恶性程度的增加，NKG2A蛋白表达逐渐升高；同时淋巴结有转移患者及临床分期为Ⅲ/Ⅳ期患者的NKG2A蛋白表达显著增高，提示NKG2A蛋白高表达与肺腺癌的恶性进展密切相关。本研究还显示NKG2A蛋白表达阳性者的5年生存率及中位生存时间均显著低于表达阴性者，提示NKG2A蛋白可作为免疫治疗的新靶点，有效抑制其表达可能延长肺腺癌患者的生存期。
综上所述，在肺腺癌中，NKG2A通过负性调控CD8+T淋巴细胞活性，从而增加肿瘤微环境的免疫抑制状态，促进肿瘤的发生发展，抑制NKG2A可能是肺腺癌免疫治疗的潜在靶点之一，在肺腺癌的临床治疗方面具有十分重要的科学理论意义和广泛的应用前景。
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