Top

Published in:

01-10-2014 | Research

Ectopic lymphoid structures in primary cutaneous melanoma

Authors: Andrea Ladányi, Tímea Sebestyén, Anita Mohos, Gabriella Liszkay, Beáta Somlai, Erika Tóth, József Tímár

Published in: Pathology & Oncology Research | Issue 4/2014

Abstract

Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO⁺ memory T cells. A network of CD21⁺ follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79⁺ HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures. The appearance of B-cell aggregates did not show association with the outcome of the disease, although a trend for their higher prevalence was observed in thicker tumors. Our results show that neogenesis of lymphoid structures does occur in primary melanomas, albeit with lower frequency compared to that reported in metastases.

Bell D, Chomarat P, Broyles D, Netto G, Moumneh Harb G, Lebecque S, Valladeau J, Davoust J, Palucka KA, Banchereau J (1999) In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 10:1417–1425CrossRef

Bombardieri M, Barone F, Humby F, Kelly S, McGurk M, Morgan P, Challacombe S, De Vita S, Valesini G, Spencer J, Pitzalis C (2007) Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren’s syndrome. J Immunol 179:4929–4938PubMedCrossRef

Cipponi A, Mercier M, Seremet T, Baurain JF, Théate I, van den Oord J, Stas M, Boon T, Coulie PG, van Baren N (2012) Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases. Cancer Res 72:3997–4007PubMedCrossRef

Coppola D, Nebozhyn M, Khalil F, Dai H, Yeatman T, Loboda A, Mulé JJ (2011) Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol 179:37–45PubMedCrossRefPubMedCentral

Coronella-Wood JA, Hersh EM (2003) Naturally occurring B-cell responses to breast cancer. Cancer Immunol Immunother 52:715–738PubMedCrossRef

de Chaisemartin L, Goc J, Damotte D, Validire P, Magdeleinat P, Alifano M, Cremer I, Fridman WH, Sautès-Fridman C, Dieu-Nosjean MC (2011) Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer. Cancer Res 71:6391–6399PubMedCrossRef

Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, Rabbe N, Laurans L, Tartour E, de Chaisemartin L, Lebecque S, Fridman WH, Cadranel J (2008) Long-term survival for patients with non–small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 26:4410–4417PubMedCrossRef

Iwamoto M, Shinohara H, Miyamoto A, Okuzawa M, Mabuchi H, Nohara T, Gon G, Toyoda M, Tanigawa N (2003) Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. Int J Cancer 104:92–97PubMedCrossRef

Jensen TO, Schmidt H, Møller HJ, Donskov F, Høyer M, Sjoegren P, Christensen IJ, Steiniche T (2012) Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer 118:2476–2485PubMedCrossRef

10.

Kirk CJ, Hartigan-O’Connor D, Mulé JJ (2001) The dynamics of the T-cell antitumor response: Chemokine-secreting dendritic cells can prime tumor-reactive T cells extranodally. Cancer Res 61:8794–8802PubMed

11.

Ladányi A, Kiss J, Mohos A, Somlai B, Liszkay G, Gilde K, Fejős Z, Gaudi I, Dobos J, Tímár J (2011) Prognostic impact of B-cell density in cutaneous melanoma. Cancer Immunol Immunother 60:1729–1738PubMedCrossRef

12.

Ladányi A, Kiss J, Somlai B, Gilde K, Fejős Z, Mohos A, Gaudi I, Tímár J (2007) Density of DC-LAMP⁺ mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother 56:1459–1469PubMedCrossRef

13.

Martinet L, Le Guellec S, Filleron T, Lamant L, Meyer N, Rochaix P, Garrido I, Girard JP (2012) High endothelial venules (HEVs) in human melanoma lesions. Major gateways for tumor-infiltrating lymphocytes. OncoImmunology 1:829–839

14.

Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, Schell MJ, Sondak VK, Weber JS, Mulé JJ (2012) 12-chemokine gene signature identifies lymph node-like structures in melanoma: Potential for patient selection for immunotherapy? Sci Rep 2:765PubMedCrossRefPubMedCentral

15.

Miyagawa S, Soeda J, Takagi S, Miwa S, Ichikawa E, Noike T (2004) Prognostic significance of mature dendritic cells and factors associated with their accumulation in metastatic liver tumors from colorectal cancer. Hum Pathol 35:1392–1396PubMedCrossRef

16.

Moldenhauer G, Popov SW, Wotschke B, Brüderlein S, Riedl P, Fissolo N, Schirmbeck R, Ritz O, Möller P, Leithäuser F (2006) AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies. Blood 107:2470–2473PubMedCrossRef

17.

Nzula S, Going JJ, Stott DI (2003) Antigen-driven clonal proliferation, somatic hypermutation, and selection of B lymphocytes infiltrating human ductal breast carcinomas. Cancer Res 63:3275–3280PubMed

18.

O’Brien PM, Tsirimonaki E, Coomber DW, Millan DW, Davis JA, Campo MS (2001) Immunoglobulin genes expressed by B-lymphocytes infiltrating cervical carcinoma show evidence of antigen-driven selection. Cancer Immunol Immunother 50:523–532PubMedCrossRef

19.

Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen Y-T, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8⁺ tumor-infiltrating lymphocytes and a high CD8⁺/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102:18538–18543PubMedCrossRefPubMedCentral

20.

Suzuki A, Masuda A, Nagata H, Kameoka S, Kikawada Y, Yamakawa M, Kasajima T (2002) Mature dendritic cells make clusters with T cells in the invasive margin of colorectal carcinoma. J Pathol 196:37–43PubMedCrossRef

21.

Thompson ED, Enriquez HL, Fu YX, Engelhard VH (2010) Tumor masses support naïve T cell infiltration, activation, and differentiation into effectors. J Exp Med 207:1791–1804PubMedCrossRefPubMedCentral

22.

Tsukayama S, Omura K, Yoshida K, Tanaka Y, Watanabe G (2005) Prognostic value of CD83-positive mature dendritic cells and their relation to vascular endothelial growth factor in advanced human gastric cancer. Oncol Rep 14:369–375PubMed

23.

van Baren N, Baurain JF, Coulie PG (2013) Lymphoid neogenesis in melanoma. What does it tell us? OncoImmunology 2:e22505

Title: Ectopic lymphoid structures in primary cutaneous melanoma
Authors: Andrea Ladányi
Tímea Sebestyén
Anita Mohos
Gabriella Liszkay
Beáta Somlai
Erika Tóth
József Tímár
Publication date: 01-10-2014
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 4/2014
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-014-9784-8

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Regional Bias of Intratumoral Genetic Heterogeneity of Nucleotide Repeats in Colon Cancers with Microsatellite Instability

The Application of Real-Time PCR Technique to Detect Rare Cell Clones with Primary T790M Substitution of EGFR Gene in Metastases of Non-small Cell Lung Cancer to Central Nervous System in Chemotherapy Naive Patients

Treatment of Refractory Hairy Cell Leukemia with a BRAF-inhibitor: Lessons to be Learnt

Oxidative DNA Damage as a Potential Early Biomarker of Helicobacter pylori Associated Carcinogenesis

Frequency of Genetic and Epigenetic Alterations of p14ARF and p16INK4A in Head and Neck Cancer in a Hungarian Population

Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer