CD8~+肿瘤浸润淋巴细胞与乳腺癌预后的关系
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摘要
目的:探讨CD8+肿瘤浸润淋巴细胞(TIL)与乳腺癌患者临床病理特征及生存期的关系。方法:用免疫组化法检测112例乳腺癌肿瘤切片CD8+TIL的表达;根据表达情况将患者分为CD8+TIL阳性组与CD8+TIL阴性组,分析CD8+TIL与临床病理特征及生存期的关系。结果:乳腺癌标本中CD8+TIL阳性率为32.14%(36/112)。统计分析显示,CD8+TIL的表达在肿瘤分化程度、TNM分期及组织学分类的组间差异有统计学意义(χ2=6.277,P=0.043;χ2=3.963,P=0.047;χ2=4.299,P=0.038);CD8+TIL阳性组5年生存率明显高于CD8+TIL阴性组(88.89%vs.71.05%;χ2=4.360,P=0.037);Log-rank检验表明CD8+TIL阳性组总生存率明显高于CD8+TIL阴性组(P=0.043)。结论:乳腺癌组织CD8+TIL可以作为患者预后的指标,癌组织中CD8+TIL低密度浸润提示预后不良。
Objective: To investigate the relations of CD8+tumor-iniltrating lymphocytes(TILs) in breast cancer patients with their clinicopathologic features and survival outcomes. Methods: The CD8+TILs expression in embedded tissue sections from 122 breast cancer patients was detected by immunohistochemical staining. According to the CD8+TILs expression status, patients were divided into CD8+TILs positive group and CD8+TILs negative group, and the relations of CD8+TILs with clinicopathologic features and survival outcomes were analyzed. Results: Among the specimens, the positive rate of CD8+TILs expression was 32.14%(36/112). Statisticalanalysis showed that the differences in CD8+TILs expression had statistical significance between or among the groups divided by degree of diferentiation(χ2=6.277, P=0.043), TNM stage(χ2=3.963, P=0.047), and histological classiication(χ2=4.299, P=0.038). The 5-year survival of CD8+TILs positive group was significantly higher than that of CD8+TILs negative group(88.89% vs. 71.05%, χ2=4.360, P=0.037). Log-rank test showed that the overall survival of CD8+TILs positive group was significantly higher than that of CD8+ TILs negative group(P=0.043). Conclusion: CD8+TILs can be used as a prognostic index for breast cancer patients and low iniltration of CD8+TILs in tumor tissue may predict a poor outcome.
Objective: To investigate the relations of CD8+tumor-iniltrating lymphocytes(TILs) in breast cancer patients with their clinicopathologic features and survival outcomes. Methods: The CD8+TILs expression in embedded tissue sections from 122 breast cancer patients was detected by immunohistochemical staining. According to the CD8+TILs expression status, patients were divided into CD8+TILs positive group and CD8+TILs negative group, and the relations of CD8+TILs with clinicopathologic features and survival outcomes were analyzed. Results: Among the specimens, the positive rate of CD8+TILs expression was 32.14%(36/112). Statisticalanalysis showed that the differences in CD8+TILs expression had statistical significance between or among the groups divided by degree of diferentiation(χ2=6.277, P=0.043), TNM stage(χ2=3.963, P=0.047), and histological classiication(χ2=4.299, P=0.038). The 5-year survival of CD8+TILs positive group was significantly higher than that of CD8+TILs negative group(88.89% vs. 71.05%, χ2=4.360, P=0.037). Log-rank test showed that the overall survival of CD8+TILs positive group was significantly higher than that of CD8+ TILs negative group(P=0.043). Conclusion: CD8+TILs can be used as a prognostic index for breast cancer patients and low iniltration of CD8+TILs in tumor tissue may predict a poor outcome.
引文
[1]Siegel R,Naishadham D,Jemal A.Cancer statistics,2013[J].CA Cancer J Clin,2013,63(1):11-30.
[2]Canna K,McArdle PA,McMillan DC,et al.The relationship between tumour T-lymphocyte infiltration,the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer[J].Br J Cancer,2005,92(4):651-654.
[3]王昆华,龚昆梅,张勇学,等.CD1D基因与B7-1基因共转染胰腺癌细胞及其抗癌作用的实验研究[J].中国普通外科杂志,2007,16(5):442-445.
[4]雷晓,石彦,余佩武,等.树突状细胞诱导抗胃癌免疫效应的实验研究[J].中国普通外科杂志,2002,11(4):230-232.
[5]Tsuta K,Ishii G,Kim E,et al.Primary lung adenocarcinoma with massive lymphocyte infiltration[J].Am J Clin Pathol,2005,123(4):547-552.
[6]Schillaci R,Salatino M,Cassataro J,et al.Immunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+response involving Fas/Fas ligand cytotoxic pathway[J].J Immunol,2006,176(6):3426-3437.
[7]Reim D,Loos M,Vogl F,et al.Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer:the Western experience of patients treated in a single-center European institution[J].J Clin Oncol,2013,31(2):263-271.
[8]Kohlberger PD,Breitenecker F,Kaider A,et al.Modified truecolor computer-assisted image analysis versus subjective scoring of estrogen receptor expression in breast cancer:a comparison[J].Anticancer Res,1999,19(3B):2189-2193.
[9]Liu S,Lachapelle J,Leung S,et al.CD8+lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer[J].Breast Cancer Res,2012,14(2):R48.
[10]Cao X.Regulatory T cells and immune tolerance to tumors[J].Immunol Res,2010,46(1-3):79-93.
[11]Lee S,Margolin K.Tumor-infiltrating lymphocytes in melanoma[J].Curr Oncol Rep,2012,14(5):468-474.
[12]Zhang L,Conejo-Garcia JR,Katsaros D,et al.Intratumoral T cells,recurrence,and survival in epithelial ovarian cancer[J].N Engl J Med,2003,348(3):203-213.
[13]杨伟明,赵洪远,王超宇,等.大肠癌肿瘤浸润CD4和CD8 T淋巴细胞的表达与预后的关系[J].中国普通外科杂志,2011,20(10):1062-1066.
[14]Pagès F,Berger A,Camus M,et al.Effector memory T cells,early metastasis,and survival in colorectal cancer[J].N Engl J Med,2005,353(25):2654-2666.
[15]Lee AH,Gillett CE,Ryder K,et al.Different patterns of inflammation and prognosis in invasive carcinoma of the breast[J].Histopathology,2006,48(6):692-701.
[16]Matkowski R,Gisterek I,Halon A,et al.The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer[J].Anticancer Res,2009,29(7):2445-2451.
[17]Camp BJ,Dyhrman ST,Memoli VA,et al.In situ cytokine production by breast cancer tumor-infiltrating lymphocytes[J].Ann Surg Oncol,1996,3(2):176-184.
[18]Mahmoud SM,Paish EC,Powe DG,et al.Tumor-infiltrating CD8+lymphocytes predict clinical outcome in breast cancer[J].J Clin Oncol,2011,29(15):1949-1955.
[19]Smyth MJ,Dunn GP,Schreiber RD.Cancer immunosurveillance and immunoediting:the roles of immunity in suppressing tumor development and shaping tumor immunogenicity[J].Adv Immunol,2006,90:1-50.
[20]Pedersen AE,Stryhn A,Justesen S,et al.Wildtype p53-specific antibody and T-cell responses in cancer patients[J].J Immunother,2011,34(9):629-640.
[2]Canna K,McArdle PA,McMillan DC,et al.The relationship between tumour T-lymphocyte infiltration,the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer[J].Br J Cancer,2005,92(4):651-654.
[3]王昆华,龚昆梅,张勇学,等.CD1D基因与B7-1基因共转染胰腺癌细胞及其抗癌作用的实验研究[J].中国普通外科杂志,2007,16(5):442-445.
[4]雷晓,石彦,余佩武,等.树突状细胞诱导抗胃癌免疫效应的实验研究[J].中国普通外科杂志,2002,11(4):230-232.
[5]Tsuta K,Ishii G,Kim E,et al.Primary lung adenocarcinoma with massive lymphocyte infiltration[J].Am J Clin Pathol,2005,123(4):547-552.
[6]Schillaci R,Salatino M,Cassataro J,et al.Immunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+response involving Fas/Fas ligand cytotoxic pathway[J].J Immunol,2006,176(6):3426-3437.
[7]Reim D,Loos M,Vogl F,et al.Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer:the Western experience of patients treated in a single-center European institution[J].J Clin Oncol,2013,31(2):263-271.
[8]Kohlberger PD,Breitenecker F,Kaider A,et al.Modified truecolor computer-assisted image analysis versus subjective scoring of estrogen receptor expression in breast cancer:a comparison[J].Anticancer Res,1999,19(3B):2189-2193.
[9]Liu S,Lachapelle J,Leung S,et al.CD8+lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer[J].Breast Cancer Res,2012,14(2):R48.
[10]Cao X.Regulatory T cells and immune tolerance to tumors[J].Immunol Res,2010,46(1-3):79-93.
[11]Lee S,Margolin K.Tumor-infiltrating lymphocytes in melanoma[J].Curr Oncol Rep,2012,14(5):468-474.
[12]Zhang L,Conejo-Garcia JR,Katsaros D,et al.Intratumoral T cells,recurrence,and survival in epithelial ovarian cancer[J].N Engl J Med,2003,348(3):203-213.
[13]杨伟明,赵洪远,王超宇,等.大肠癌肿瘤浸润CD4和CD8 T淋巴细胞的表达与预后的关系[J].中国普通外科杂志,2011,20(10):1062-1066.
[14]Pagès F,Berger A,Camus M,et al.Effector memory T cells,early metastasis,and survival in colorectal cancer[J].N Engl J Med,2005,353(25):2654-2666.
[15]Lee AH,Gillett CE,Ryder K,et al.Different patterns of inflammation and prognosis in invasive carcinoma of the breast[J].Histopathology,2006,48(6):692-701.
[16]Matkowski R,Gisterek I,Halon A,et al.The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer[J].Anticancer Res,2009,29(7):2445-2451.
[17]Camp BJ,Dyhrman ST,Memoli VA,et al.In situ cytokine production by breast cancer tumor-infiltrating lymphocytes[J].Ann Surg Oncol,1996,3(2):176-184.
[18]Mahmoud SM,Paish EC,Powe DG,et al.Tumor-infiltrating CD8+lymphocytes predict clinical outcome in breast cancer[J].J Clin Oncol,2011,29(15):1949-1955.
[19]Smyth MJ,Dunn GP,Schreiber RD.Cancer immunosurveillance and immunoediting:the roles of immunity in suppressing tumor development and shaping tumor immunogenicity[J].Adv Immunol,2006,90:1-50.
[20]Pedersen AE,Stryhn A,Justesen S,et al.Wildtype p53-specific antibody and T-cell responses in cancer patients[J].J Immunother,2011,34(9):629-640.