Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma
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Background: Programmed death-1 (PD-1) is physiologically expressed by germinal center-asso-ciated helper T-cells and has an inhibitory effect on T-cell activity. Methods: We examined 63 cas¬es of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal an¬tibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400×). Results: Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (≤20/HPF, n=30). The for¬mer group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score. Conclusions: The high number of PD-1-positive cells might be associated with an unfavorable outcome in DL¬BCL patients.
Abstract
Background: Programmed death-1 (PD-1) is physiologically expressed by germinal center-asso-ciated helper T-cells and has an inhibitory effect on T-cell activity. Methods: We examined 63 cas¬es of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal an¬tibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400×). Results: Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (≤20/HPF, n=30). The for¬mer group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score. Conclusions: The high number of PD-1-positive cells might be associated with an unfavorable outcome in DL¬BCL patients.
참고문헌 (28)
- "A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project", Blood, 89, pp.3909~3918 (1997)
- Coiffier B, "Diffuse large cell lymphoma", Curr Opin Oncol, 13, pp.325~334 (2001)
- Swerdlow SH, "WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed", pp.233~243 (2008), IARC Press
- Coiffier B, "CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma", N Engl J Med, 346, pp.235~242 (2002)
- Feugier P, "Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte", J Clin Oncol, 23, pp.4117~4126 (2005)
- Pfreundschuh M, "CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group", Lancet Oncol, 7, pp.379~391 (2006)
- "A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project", N Engl J Med, 329, pp.987~994 (1993)
- Bairey O, "Bcl-2, Bcl-X, Bax, and Bak expression in short- and long-lived patients with diffuse large B-cell lymphomas", Clin Cancer Res, 5, pp.2860~2866 (1999)
- Hermine O, "Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin’s lymphoma. Groupe d’Etude des Lymphomes de l’Adulte (GELA)", Blood, 87, pp.265~272 (1996)
- Colomo L, "Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma", Blood, 101, pp.78~84 (2003)
- Kramer MH, "Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study", J Clin Oncol, 14, pp.2131~2138 (1996)
- Kramer MH, "Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma", Blood, 92, pp.3152~3162 (1998)
- Morgan G, "Changing trends in the incidence of non-Hodgkin’s lymphoma in Europe. Biomed Study Group", Ann Oncol, 8(Suppl 2), pp.49~54 (1997)
- 김동철, "미만성 대세포 B 림프종에서 P53, BCL-2 단백 발현 및 세포증식지수와 국제예후지표와의 연관성 분석", The Korean Journal of Pathology, 37(6), pp.407~412 (2003), 대한병리학회
- Alizadeh AA, "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling", Nature, 403, pp.503~511 (2000)
- Barrans SL, "Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma", Blood, 99, pp.1136~1143 (2002)
- Chang CC, "Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma", Am J Surg Pathol, 28, pp.464~470 (2004)
- Hans CP, "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray", Blood, 103, pp.275~282 (2004)
- Linderoth J, "Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Study", Clin Cancer Res, 9, pp.722~728 (2003)
- Greenwald RJ, "The B7 family revisited", Annu Rev Immunol, 23, pp.515~548 (2005)
- Riley JL, "The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation", Blood, 105, pp.13~21 (2005)
- Keir ME, "PD-1 and its ligands in T-cell immunity", Curr Opin Immunol, 19, pp.309~314 (2007)
- Carreras J, "High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma", J Clin Oncol, 27, pp.1470~1476 (2009)
- Muenst S, "Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival", Hum Pathol, 40, pp.1715~1722 (2009)
- Hsu MC, "Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma", Mod Pathol, 23, pp.1393~1403 (2010)
- Thompson RH, "PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma", Clin Cancer Res, 13, pp.1757~1761 (2007)
- Young Ha Oh, "Prognostic Evaluation of Nodal Diffuse Large B Cell Lymphoma by Immunohistochemical Profiles with Emphasis on CD138 Expression as a Poor Prognostic Factor", Journal of Korean Medical Science, 21(3), pp.397~405 (2006), 대한의학회
- Tzankov A, "Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma", Haematologica, 93, pp.193~200 (2008)
