Clinicopathologic significance of tumor microenvironment CD11c, and FOXP3 expression in diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors’ microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy. Methods: The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors’ microenvironment were evaluated using an immunohistochemistry (IHC). Results: CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival (p = 0.019) and overall survival (p = 0.039) between the two groups. Conclusions: We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.
Abstract
Background/Aims: CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors’ microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy. Methods: The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors’ microenvironment were evaluated using an immunohistochemistry (IHC). Results: CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival (p = 0.019) and overall survival (p = 0.039) between the two groups. Conclusions: We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.
참고문헌 (37)
- Coiffier B., "Diffuse large cell lymphoma", Curr Opin Oncol, 13, pp.325~334 (2001)
- Rossi D, "Molecular heterogeneity of diffuse large B-cell lymphoma: implications for disease management and prognosis", Hematology, 7, pp.239~252 (2002)
- Lenz G, "Stromal gene signatures in large-B-cell lymphomas", N Engl J Med, 359, pp.2313~2323 (2008)
- Akay OM, "BCL2, BCL6, IGH, TP53, and MYC protein expression and gene rearrangements as prognostic markers in diffuse large B-cell lymphoma: a study of 44 Turkish patients", Cancer Genet, 207, pp.87~93 (2014)
- Liotta LA, "The microenvironment of the tumour-host interface", Nature, 411, pp.375~379 (2001)
- Schreiber RD, "Cancer immunoediting:integrating immunity’s roles in cancer suppression and promotion", Science, 331, pp.1565~1570 (2011)
- Fontenot JD, "A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3", Nat Immunol, 6, pp.331~337 (2005)
- 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)
- Beyer M, "Regulatory T cells in cancer", Blood, 108, pp.804~811 (2006)
- Banchereau J, "Dendritic cells and the control of immunity", Nature, 392, pp.245~252 (1998)
- Banchereau J, "Immunobiology of dendritic cells", Annu Rev Immunol, 18, pp.767~811 (2000)
- Lanzavecchia A, "The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics", Curr Opin Immunol, 13, pp.291~298 (2001)
- Gabrilovich D., "Mechanisms and functional significance of tumour-induced dendritic-cell defects", Nat Rev Immunol, 4, pp.941~952 (2004)
- Dubsky P, "Human dendritic cell subsets for vaccination", J Clin Immunol, 25, pp.551~572 (2005)
- Steinman RM, "Taking dendritic cells into medicine", Nature, 449, pp.419~426 (2007)
- Palucka K, "Designing vaccines based on biology of human dendritic cell subsets", Immunity, 33, pp.464~478 (2010)
- Shortman K, "Mouse and human dendritic cell subtypes", Nat Rev Immunol, 2, pp.151~161 (2002)
- Spits H, "Natural killer or dendritic: what’s in a name?", Immunity, 26, pp.11~16 (2007)
- Campo E, "The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications", Blood, 117, pp.5019~5032 (2011)
- 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)
- Sweetenham JW., "Diffuse large B-cell lymphoma : risk stratification and management of relapsed disease", Hematology Am Soc Hematol Educ Program, pp.252~259 (2005)
- Alizadeh AA, "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling", Nature, 403, pp.503~511 (2000)
- Shiozawa E, "The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries", Leuk Res, 31, pp.1579~1583 (2007)
- 황희상, "Prognostic value of immunohistochemical algorithms in gastrointestinal diffuse large B-cell lymphoma", Blood Research, 48(4), pp.266~273 (2013), 대한혈액학회
- Lopez-Guillermo A, "Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin", J Clin Oncol, 23, pp.2797~2804 (2005)
- Abramson JS, "Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach", Blood, 106, pp.1164~1174 (2005)
- Moller MB, "Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation: a population-based study of 1575cases", Br J Haematol, 124, pp.151~159 (2004)
- d’Amore F, "Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group", Eur J Cancer, 27, pp.1201~1208 (1991)
- Houldsworth J, "REL proto-oncogene is frequently amplified in extranodal diffuse large cell lymphoma", Blood, 87, pp.25~29 (1996)
- Gronbaek K, "Somatic Fas mutations in non-Hodgkin’s lymphoma: association with extranodal disease and autoimmunity", Blood, 92, pp.3018~3024 (1998)
- Sakaguchi S, "Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases", J Immunol, 155, pp.1151~1164 (1995)
- Li B, "FOXP3 ensembles in T-cell regulation", Immunol Rev, 212, pp.99~113 (2006)
- Coutinho R, "Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry:robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP", Haematologica, 100, pp.363~369 (2015)
- Lee NR, "Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis", Leuk Lymphoma, 49, pp.247~256 (2008)
- Shurin MR, "Intratumoral cytokines", chemokines, Cancer Metastasis Rev, pp.2006, 25[DOI]
- Middle S, "Immunohistochemical analysis indicates that the anatomical location of B-cell non-Hodgkin’s lymphoma is determined by differentially expressed chemokine receptors, sphingosine-1-phosphate receptors and integrins", Exp Hematol Oncol, 4, pp.10~ (2015)
- Upadhyay R, "Lymphoma: immune evasion strategies", Cancers (Basel), 7, pp.736~762 (2015)
