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12.04.2024 | ORIGINAL ARTICLE

Prognostic Significance of T-Cells and Macrophages in the Tumour Microenvironment of Nodal DLBCL

verfasst von: Soundarya Ravi, J. Sree Rekha, Debdatta Basu, Smita Kayal

Erschienen in: Indian Journal of Hematology and Blood Transfusion

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Abstract

Revised International Prognostic (R-IPI) score is used widely for risk stratification of DLBCL cases, yet some patients belonging to same risk category tend to exhibit different outcomes. The role of T-cells and macrophages in prognostication of lymphomas has been a point of interest of late. We aimed to study the association of FOXP3 positive T-regulatory cells, cytotoxic T-cells and macrophages with the immunophenotypic subtypes, clinicopathological characteristics, treatment response and survival in nodal diffuse large B-cell lymphoma (DLBCL) patients. The clinicopathological and treatment data of 83 DLBCL patients diagnosed and treated at our institute from January 2015 to December 2018 were collected and followed up till June 2020. CD8, FOXP3 and CD68 immunostains were performed to highlight the cytotoxic T-cells, T-regulatory cells and macrophages respectively on the lymph node biopsies and the distribution of these cells and their association with clinico-pathological factors, treatment response and survival was analyzed. DLBCL cases with higher percentage of CD3 positive T-cells and CD8 positive cytotoxic T-cells had significant association with attainment of complete response to treatment. In addition, CD8 positive T-cells of more than 6.5% proved to be an independent predictor of treatment outcome (p = 0.022). Multivariate Cox regression survival analysis revealed that cases with ‘good’ R-IPI prognostic score and ‘high CD68 positive macrophages in tumor microenvironment’ had a significantly longer overall survival. Increased number of cytotoxic T-cells was significantly associated with complete response to treatment and higher number of macrophages correlated significantly with better overall survival signifying their antitumor effects.
Literatur
1.
Zurück zum Zitat Swerdlow SH, Campo E, Harris NL (2017) WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed. IARC, Lyon, p.291–7 Swerdlow SH, Campo E, Harris NL (2017) WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed. IARC, Lyon, p.291–7
2.
Zurück zum Zitat Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW et al (2008) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319:1676–1679CrossRefPubMed Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW et al (2008) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319:1676–1679CrossRefPubMed
3.
Zurück zum Zitat Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242CrossRefPubMed Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242CrossRefPubMed
4.
Zurück zum Zitat Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P et al (2007) The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 109:1857–1861CrossRefPubMed Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P et al (2007) The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 109:1857–1861CrossRefPubMed
5.
Zurück zum Zitat Scott DW, Gascoyne RD (2014) The tumor microenvironment in B cell lymphomas. Nat Rev Cancer 14:517–534CrossRefPubMed Scott DW, Gascoyne RD (2014) The tumor microenvironment in B cell lymphomas. Nat Rev Cancer 14:517–534CrossRefPubMed
6.
Zurück zum Zitat de Jong D, Enblad G (2008) Inflammatory cells and immune microenvironment in malignant lymphoma. J Intern Med 264:528–536CrossRefPubMed de Jong D, Enblad G (2008) Inflammatory cells and immune microenvironment in malignant lymphoma. J Intern Med 264:528–536CrossRefPubMed
7.
Zurück zum Zitat Muris JJF, Meijer CJLM, Cillessen S a. GM, Vos W, Kummer JA, Bladergroen BA, et al (2004) Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas. Leukemia 18:589–96. Muris JJF, Meijer CJLM, Cillessen S a. GM, Vos W, Kummer JA, Bladergroen BA, et al (2004) Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas. Leukemia 18:589–96.
9.
Zurück zum Zitat Tzankov A, Meier C, Hirschmann P, Went P, Pileri SA, Dirnhofer S (2008) 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 93:193–200CrossRefPubMed Tzankov A, Meier C, Hirschmann P, Went P, Pileri SA, Dirnhofer S (2008) 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 93:193–200CrossRefPubMed
10.
Zurück zum Zitat Zou W (2006) Regulatory T cells, tumor immunity and immunotherapy. Nat Rev Immunol 6:295–307CrossRefPubMed Zou W (2006) Regulatory T cells, tumor immunity and immunotherapy. Nat Rev Immunol 6:295–307CrossRefPubMed
12.
Zurück zum Zitat Riihijärvi S, Fiskvik I, Taskinen M, Vajavaara H, Tikkala M, Yri O et al (2015) Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial. Haematologica 100:238–245CrossRefPubMedPubMedCentral Riihijärvi S, Fiskvik I, Taskinen M, Vajavaara H, Tikkala M, Yri O et al (2015) Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial. Haematologica 100:238–245CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Hasselblom S, Hansson U, Sigurdardottir M, Nilsson-Ehle H, Ridell B, Andersson P-O (2008) Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis. Pathol Int 58:529–532CrossRefPubMed Hasselblom S, Hansson U, Sigurdardottir M, Nilsson-Ehle H, Ridell B, Andersson P-O (2008) Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis. Pathol Int 58:529–532CrossRefPubMed
14.
Zurück zum Zitat Meyer PN, Fu K, Greiner T, Smith L, Delabie J, Gascoyne R et al (2011) The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol 135:54–61CrossRefPubMed Meyer PN, Fu K, Greiner T, Smith L, Delabie J, Gascoyne R et al (2011) The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol 135:54–61CrossRefPubMed
15.
Zurück zum Zitat Olweny CL (1990) Cotswolds modification of the Ann Arbor staging system for Hodgkin’s disease. J Clin Oncol 8:1598–1598PubMed Olweny CL (1990) Cotswolds modification of the Ann Arbor staging system for Hodgkin’s disease. J Clin Oncol 8:1598–1598PubMed
16.
Zurück zum Zitat Cheson BD (2015) Staging and response assessment in lymphomas: the new Lugano classification. Chin Clin Oncol 4:5PubMed Cheson BD (2015) Staging and response assessment in lymphomas: the new Lugano classification. Chin Clin Oncol 4:5PubMed
17.
Zurück zum Zitat El-Galaly TC, Villa D, Alzahrani M, Hansen JW, Sehn LH, Wilson D et al (2015) Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: a Danish-Canadian study of 443 patients with diffuse-large B-cell lymphoma. Am J Hematol 90:1041–1046CrossRefPubMed El-Galaly TC, Villa D, Alzahrani M, Hansen JW, Sehn LH, Wilson D et al (2015) Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: a Danish-Canadian study of 443 patients with diffuse-large B-cell lymphoma. Am J Hematol 90:1041–1046CrossRefPubMed
18.
Zurück zum Zitat Chang K-C, Huang G-C, Jones D, Lin Y-H (2007) Distribution patterns of dendritic cells and T cells in diffuse large B-cell lymphomas correlate with prognoses. Clin Cancer Res 13:6666–6672CrossRefPubMed Chang K-C, Huang G-C, Jones D, Lin Y-H (2007) Distribution patterns of dendritic cells and T cells in diffuse large B-cell lymphomas correlate with prognoses. Clin Cancer Res 13:6666–6672CrossRefPubMed
19.
Zurück zum Zitat Linderoth J, Edén P, Ehinger M, Valcich J, Jerkeman M, Bendahl P-O et al (2008) Genes associated with the tumor microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma. Br J Haematol 141:423–432CrossRefPubMed Linderoth J, Edén P, Ehinger M, Valcich J, Jerkeman M, Bendahl P-O et al (2008) Genes associated with the tumor microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma. Br J Haematol 141:423–432CrossRefPubMed
20.
Zurück zum Zitat Lippman S, Spier C, Miller T, Slymen D, Rybski J, Grogan T (1990) Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. Mod Pathol 3:361–367PubMed Lippman S, Spier C, Miller T, Slymen D, Rybski J, Grogan T (1990) Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. Mod Pathol 3:361–367PubMed
21.
Zurück zum Zitat Hasselblom S, Sigurdadottir M, Hansson U, Nilsson-Ehle H, Ridell B, Andersson P-O (2007) The number of tumor-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+ regulatory T cells predicts outcome in diffuse large B-cell lymphoma. Br J Haematol 137:364–373CrossRefPubMed Hasselblom S, Sigurdadottir M, Hansson U, Nilsson-Ehle H, Ridell B, Andersson P-O (2007) The number of tumor-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+ regulatory T cells predicts outcome in diffuse large B-cell lymphoma. Br J Haematol 137:364–373CrossRefPubMed
22.
Zurück zum Zitat Nam SJ, Go H, Paik JH, Kim TM, Heo DS, Kim CW et al (2014) An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma 55:2466–2476CrossRefPubMed Nam SJ, Go H, Paik JH, Kim TM, Heo DS, Kim CW et al (2014) An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma 55:2466–2476CrossRefPubMed
23.
Zurück zum Zitat Wada N, Zaki MAA, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y et al (2012) Tumor-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. Histopathology 60:313–319CrossRefPubMed Wada N, Zaki MAA, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y et al (2012) Tumor-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. Histopathology 60:313–319CrossRefPubMed
24.
Zurück zum Zitat Li Y-L, Shi Z-H, Wang X, Gu K-S, Zhai Z-M (2019) Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count. BMC Cancer 19:1049CrossRefPubMedPubMedCentral Li Y-L, Shi Z-H, Wang X, Gu K-S, Zhai Z-M (2019) Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count. BMC Cancer 19:1049CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Lee N-R, Song E-K, Jang KY, Choi HN, Moon WS, Kwon K et al (2008) Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma 49:247–256CrossRefPubMed Lee N-R, Song E-K, Jang KY, Choi HN, Moon WS, Kwon K et al (2008) Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma 49:247–256CrossRefPubMed
26.
Zurück zum Zitat Serag El-Dien MM, Abdou AG, Asaad NY, Abd El-Wahed MM, Kora MAE-HM. (2017) Intratumoral FOXP3+ regulatory T cells in diffuse large B-cell lymphoma. Appl Immunohistochem Mol Morphol 25:534–42 Serag El-Dien MM, Abdou AG, Asaad NY, Abd El-Wahed MM, Kora MAE-HM. (2017) Intratumoral FOXP3+ regulatory T cells in diffuse large B-cell lymphoma. Appl Immunohistochem Mol Morphol 25:534–42
Metadaten
Titel
Prognostic Significance of T-Cells and Macrophages in the Tumour Microenvironment of Nodal DLBCL
verfasst von
Soundarya Ravi
J. Sree Rekha
Debdatta Basu
Smita Kayal
Publikationsdatum
12.04.2024
Verlag
Springer India
Erschienen in
Indian Journal of Hematology and Blood Transfusion
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-024-01770-6

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