肿瘤相关巨噬细胞的极化与原发性胃肠道弥漫大B细胞淋巴瘤复发的相关性分析
|
摘要
目的:检测肿瘤相关巨噬细胞(TAM)分子表面标志物CD68、CD206在胃肠道弥漫大B细胞淋巴瘤(PGI-DLBCL)初诊和首次复发的表达变化,分析其变化与临床相关参数的关系,探讨TAM的极化在PGI-DLBCL复发中的作用。方法:收集28例PGI-DLBCL患者初诊和首次复发后淋巴瘤标本,采用免疫组织化学法分别检测TAM的分子标志物CD68和CD206的表达变化。根据CD68和CD206初诊至首次复发后表达的变化,将28例患者分为"增强"、"稳定"和"减弱"3种情况,分析其变化与临床病理参数、疾病复发的相关性。结果:CD68和CD206不同程度表达的病例所占比例间存在显著差异(P<0.05),且CD68和CD206间存在一定相关性(P=0.008)。CD68和CD206表达变化与患者年龄、性别、分期、有无B症状、病理类型、ECOG评分和IPI评分无关,CD206的表达变化与原发部位有关(P<0.05)。CD68(P=0.23)和CD206 (P=0.818)变化与肿瘤复发时间无关。结论:M2-TAM的极化促进了PGI-DLBCL复发,可能成为预测PG-DLBCL复发的相关指标。
Objective: To detect the change in expression of the tumor associated macrophage(TAM) markers CD68 and CD206 from first diagnosis to first relapse of primary gastrointestinal diffuse large B cell lymphoma(PGI-DLBCL), analyze the correlation between the changes and related clinical parameters, and explore the significance of polarization of TAM in treating the relapse. Methods: Lymphomas from 28 PGI-DLBCL patients at first diagnosis and first relapse were collected and molecular markers CD68 and CD206 were measured by immunohistochemical assay. Based on the change of CD68 and CD206, patients were categorized into three types: "increased", "stable" and "decreased". The ratio of cases with different expression level of CD68 and CD206 was compared, and the correlation among the changes, related clinical parameters and the relapse were analyzed.Results: Significant differences in ratio of cases with different expression level of CD68 and CD206 were observed(P<0.05) and there was a correlation between CD68 and CD206(P=0.008). CD68 and CD206 expression showed no correlation with age, gender, stage, B symptoms, pathological type, ECOG score, or IPI scores, while CD206 expression had a positive correlation with primary site(P<0.05). There was no correlation between the changes and time to relapse(CD68: P=0.23 and CD206: P=0.818) Conclusion: Our study suggest that polarization of M2-TAM can promote the relapse of PGI-DLBCL, and it may be an important indicator of relapse of PGI-DLBCL.
Objective: To detect the change in expression of the tumor associated macrophage(TAM) markers CD68 and CD206 from first diagnosis to first relapse of primary gastrointestinal diffuse large B cell lymphoma(PGI-DLBCL), analyze the correlation between the changes and related clinical parameters, and explore the significance of polarization of TAM in treating the relapse. Methods: Lymphomas from 28 PGI-DLBCL patients at first diagnosis and first relapse were collected and molecular markers CD68 and CD206 were measured by immunohistochemical assay. Based on the change of CD68 and CD206, patients were categorized into three types: "increased", "stable" and "decreased". The ratio of cases with different expression level of CD68 and CD206 was compared, and the correlation among the changes, related clinical parameters and the relapse were analyzed.Results: Significant differences in ratio of cases with different expression level of CD68 and CD206 were observed(P<0.05) and there was a correlation between CD68 and CD206(P=0.008). CD68 and CD206 expression showed no correlation with age, gender, stage, B symptoms, pathological type, ECOG score, or IPI scores, while CD206 expression had a positive correlation with primary site(P<0.05). There was no correlation between the changes and time to relapse(CD68: P=0.23 and CD206: P=0.818) Conclusion: Our study suggest that polarization of M2-TAM can promote the relapse of PGI-DLBCL, and it may be an important indicator of relapse of PGI-DLBCL.
引文
1 Koch P, del Valle F, Berdel WE, et al. Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92[J]. J Clin Oncol, 2001, 19(18): 3861-3873.
2 Kridel R, Steidl C,Gascoyne RD. Tumor-associated macrophages in diffuse large B-cell lymphoma[J]. Haematologica, 2015, 100(2): 143-145.
3 吴婷,周武雄. 肿瘤相关巨噬细胞的极化与肿瘤的发展[J]. 现代肿瘤医学, 2015, 23(12): 1753-1756.
4 Mantovani A, Schioppa T, Porta C, et al. Role of tumor-associated macrophages in tumor progression and invasion[J]. Cancer Metastasis Rev, 2006, 25(3): 315-322.
5 Olsson A, Nakhle J, Sundstedt A, et al. Tasquinimod triggers an early change in the polarization of tumor associated macrophages in the tumor microenvironment[J]. J Immunother Cancer, 2015, 3: 53.
6 Aras S,Zaidi MR. TAMeless traitors: macrophages in cancer progression and metastasis[J]. Br J Cancer, 2017, 117(11): 1583-1591.
7 Locatelli L, Cadamuro M, Spirli C, et al. Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis[J]. Hepatology, 2016, 63(3): 965-982.
8 Martinez FO,Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment[J]. F1000 Prime Rep, 2014, 6: 13.
9 Solinas G, Germano G, Mantovani A, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation[J]. J Leukoc Biol, 2009, 86(5): 1065-1073.
10 den Breems NY,Eftimie R. The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes[J]. J Theor Biol, 2016, 390: 23-39.
11 Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma[J]. N Engl J Med, 2010, 362(10): 875-885.
12 Nam SJ, Go H, Paik JH, et al. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone[J]. Leuk Lymphoma, 2014, 55(11): 2466-2476.
13 Marchesi F, Cirillo M, Bianchi A, et al. High density of CD68+/CD163+ tumour-associated macrophages (M2-TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B-cell lymphoma[J]. Hematol Oncol, 2015, 33(2): 110-112.
14 Hasselblom S, Hansson U, Sigurdardottir M, et al. Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis[J]. Pathol Int, 2008, 58(8): 529-532.
15 Riihijarvi S, Fiskvik I, Taskinen M, et al. Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial[J]. Haematologica, 2015, 100(2): 238-245.
16 Nakamura S, Matsumoto T, Iida M, et al. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends[J]. Cancer, 2003, 97(10): 2462-2473.
17 Guglielmi C. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial[J]. J Clin Oncol, 1998, 10(16): 3264-3269.
2 Kridel R, Steidl C,Gascoyne RD. Tumor-associated macrophages in diffuse large B-cell lymphoma[J]. Haematologica, 2015, 100(2): 143-145.
3 吴婷,周武雄. 肿瘤相关巨噬细胞的极化与肿瘤的发展[J]. 现代肿瘤医学, 2015, 23(12): 1753-1756.
4 Mantovani A, Schioppa T, Porta C, et al. Role of tumor-associated macrophages in tumor progression and invasion[J]. Cancer Metastasis Rev, 2006, 25(3): 315-322.
5 Olsson A, Nakhle J, Sundstedt A, et al. Tasquinimod triggers an early change in the polarization of tumor associated macrophages in the tumor microenvironment[J]. J Immunother Cancer, 2015, 3: 53.
6 Aras S,Zaidi MR. TAMeless traitors: macrophages in cancer progression and metastasis[J]. Br J Cancer, 2017, 117(11): 1583-1591.
7 Locatelli L, Cadamuro M, Spirli C, et al. Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis[J]. Hepatology, 2016, 63(3): 965-982.
8 Martinez FO,Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment[J]. F1000 Prime Rep, 2014, 6: 13.
9 Solinas G, Germano G, Mantovani A, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation[J]. J Leukoc Biol, 2009, 86(5): 1065-1073.
10 den Breems NY,Eftimie R. The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes[J]. J Theor Biol, 2016, 390: 23-39.
11 Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma[J]. N Engl J Med, 2010, 362(10): 875-885.
12 Nam SJ, Go H, Paik JH, et al. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone[J]. Leuk Lymphoma, 2014, 55(11): 2466-2476.
13 Marchesi F, Cirillo M, Bianchi A, et al. High density of CD68+/CD163+ tumour-associated macrophages (M2-TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B-cell lymphoma[J]. Hematol Oncol, 2015, 33(2): 110-112.
14 Hasselblom S, Hansson U, Sigurdardottir M, et al. Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis[J]. Pathol Int, 2008, 58(8): 529-532.
15 Riihijarvi S, Fiskvik I, Taskinen M, et al. Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial[J]. Haematologica, 2015, 100(2): 238-245.
16 Nakamura S, Matsumoto T, Iida M, et al. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends[J]. Cancer, 2003, 97(10): 2462-2473.
17 Guglielmi C. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial[J]. J Clin Oncol, 1998, 10(16): 3264-3269.