Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study

Authors: Ji-Young Choe, Ji Yun Yun, Yoon Kyoung Jeon, Se Hoon Kim, Gyeongsin Park, Joo Ryoung Huh, Sohee Oh, Ji Eun Kim

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Regulation of tumor microenvironment is closely involved in the prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an enzyme acting as immune modulator through suppression of T-cell immunity. This study aims to investigate role of IDO in the microenvironment of HL.

Methods

A total of 121 cases of HL were enrolled to do immunohistochemistry for IDO, CD163, CD68, CD4, CD8, and FoxP3. Positivity was evaluated from area fractions or numbers of positive cells using automated image analyzer. Correlations between IDO expression and various cellular infiltrates and clinicopathologic parameters were examined and survival analyses were performed.

Results

IDO was expressed in histiocytes, dendritic cells and some endothelial cells with variable degrees, but not in tumor cells. IDO positive cells were more frequently found in mixed cellularity type than other histologic types, and in cases with EBV+, high Ann Arbor stages, B symptoms, and high IPS (all p < 0.05). High IDO expression was associated with inferior survival (p < 0.001) and reflects an independent prognostic factor in nodular sclerosis HL.

Conclusions

This is the first study suggesting that IDO is the principle immunomodulator and is involved to adverse clinical outcomes of HL.
Appendix
Available only for authorised users
Literature
1.
Herreros B, Sanchez-Aguilera A, Piris MA: Lymphoma microenvironment: culprit or innocent?. Leukemia. 2008, 22: 49-58. 10.1038/sj.leu.2404970.CrossRefPubMed
2.
Steidl C, Connors JM, Gascoyne RD: Molecular pathogenesis of Hodgkin’s lymphoma: increasing evidence of the importance of the microenvironment. J Clin Oncol. 2011, 29: 1812-1826. 10.1200/JCO.2010.32.8401.CrossRefPubMed
3.
Wilke CM, Zou W: T lymphocytes to IDO + cells: check. Blood. 2011, 117: 2082-2083. 10.1182/blood-2010-12-322172.CrossRefPubMed
4.
Curti A, Trabanelli S, Salvestrini V, Baccarani M, Lemoli RM: The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood. 2009, 113: 2394-2401. 10.1182/blood-2008-07-144485.CrossRefPubMed
5.
Puccetti P, Grohmann U: IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat Rev Immunol. 2007, 7: 817-823. 10.1038/nri2163.CrossRefPubMed
6.
Andersen MH: The specific targeting of immune regulation: T-cell responses against indoleamine 2,3-dioxygenase. Cancer Immunol Immunother. 2012, 61: 1289-1297. 10.1007/s00262-012-1234-4.CrossRefPubMedPubMedCentral
7.
Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R: Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res. 2011, 17: 6985-6991. 10.1158/1078-0432.CCR-11-1331.CrossRefPubMed
8.
Ino K, Yamamoto E, Shibata K, Kajiyama H, Yoshida N, Terauchi M, Nawa A, Nagasaka T, Takikawa O, Kikkawa F: Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin Cancer Res. 2008, 14: 2310-2317. 10.1158/1078-0432.CCR-07-4144.CrossRefPubMed
9.
Inaba T, Ino K, Kajiyama H, Yamamoto E, Shibata K, Nawa A, Nagasaka T, Akimoto H, Takikawa O, Kikkawa F: Role of the immunosuppressive enzyme indoleamine 2,3-dioxygenase in the progression of ovarian carcinoma. Gynecol Oncol. 2009, 115: 185-192. 10.1016/j.ygyno.2009.07.015.CrossRefPubMed
10.
Lee JR: Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Lab Invest. 2003, 83: 1457-1466. 10.1097/01.LAB.0000090158.68852.D1.CrossRefPubMed
11.
Ninomiya S, Hara T, Tsurumi H, Hoshi M, Kanemura N, Goto N, Kasahara S, Shimizu M, Ito H, Saito K, Hirose Y, Yamada T, Takahashi T, Seishima M, Takami T, Moriwaki H: Indoleamine 2,3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol. 2011, 90: 409-416. 10.1007/s00277-010-1093-z.CrossRefPubMed
12.
Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD: Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010, 362: 875-885. 10.1056/NEJMoa0905680.CrossRefPubMedPubMedCentral
13.
Kamper P, Bendix K, Hamilton-Dutoit S, Honore B, Nyengaard JR, D’Amore F: Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin’s lymphoma. Haematologica. 2011, 96: 269-276. 10.3324/haematol.2010.031542.CrossRefPubMed
14.
Zaki MA, Wada N, Ikeda J, Shibayama H, Hashimoto K, Yamagami T, Tatsumi Y, Tsukaguchi M, Take H, Tsudo M, Morii E, Aozasa K: Prognostic implication of types of tumor-associated macrophages in Hodgkin lymphoma. Virchows Arch. 2011, 459: 361-366. 10.1007/s00428-011-1140-8.CrossRefPubMed
15.
Tzankov A, Matter MS, Dirnhofer S: Refined prognostic role of CD68-positive tumor macrophages in the context of the cellular micromilieu of classical Hodgkin lymphoma. Pathobiology. 2010, 77: 301-308. 10.1159/000321567.CrossRefPubMed
16.
Greaves P, Clear A, Coutinho R, Wilson A, Matthews J, Owen A, Shanyinde M, Lister TA, Calaminici M, Gribben JG: Expression of FOXP3, CD68, and CD20 at diagnosis in the microenvironment of classical Hodgkin lymphoma is predictive of outcome. J Clin Oncol. 2013, 31: 256-262. 10.1200/JCO.2011.39.9881.CrossRefPubMed
17.
Elpek KG, Lacelle C, Singh NP, Yolcu ES, Shirwan H: CD4 + CD25+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a B cell lymphoma model. J Immunol. 2007, 178: 6840-6848. 10.4049/jimmunol.178.11.6840.CrossRefPubMed
18.
Koh YW, Yoon DH, Suh C, Huh J: Impact of the Epstein-Barr virus positivity on Hodgkin’s lymphoma in a large cohort from a single institute in Korea. Ann Hematol. 2012, 91: 1403-1412. 10.1007/s00277-012-1464-8.CrossRefPubMed
19.
20.
Song H, Park H, Kim J, Park G, Kim YS, Kim SM, Kim D, Seo SK, Lee HK, Cho D, Hur D: IDO metabolite produced by EBV-transformed B cells inhibits surface expression of NKG2D in NK cells via the c-Jun N-terminal kinase (JNK) pathway. Immunol Lett. 2011, 136: 187-193. 10.1016/j.imlet.2011.01.009.CrossRefPubMed
21.
Manches O, Fernandez MV, Plumas J, Chaperot L, Bhardwaj N: Activation of the noncanonical NF-kappaB pathway by HIV controls a dendritic cell immunoregulatory phenotype. Proc Natl Acad Sci U S A. 2012, 109: 14122-14127. 10.1073/pnas.1204032109.CrossRefPubMedPubMedCentral
Metadata
Title
Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study
Authors
Ji-Young Choe
Ji Yun Yun
Yoon Kyoung Jeon
Se Hoon Kim
Gyeongsin Park
Joo Ryoung Huh
Sohee Oh
Ji Eun Kim
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-335

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

Research article

VEGFR-3 and CXCR4 as predictive markers for treatment with fluorouracil, leucovorin plus either oxaliplatin or cisplatin in patients with advanced esophagogastric cancer: a comparative study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Research article

Overexpression of prostate tumor overexpressed 1 correlates with tumor progression and predicts poor prognosis in breast cancer

Research article

Cost-effectiveness of family history-based colorectal cancer screening in Australia

Research article

CUB Domain Containing Protein 1 (CDCP1) modulates adhesion and motility in colon cancer cells

Research article

Anti-proliferative but not anti-angiogenic tyrosine kinase inhibitors enrich for cancer stem cells in soft tissue sarcoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits