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 ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer

Authors: Sebastian Lundgren, Jonna Berntsson, Björn Nodin, Patrick Micke, Karin Jirström

Published in: Journal of Ovarian Research | Issue 1/2016

Login to get access

Abstract

Background

The critical role of the immune system in controlling cancer progression has become evident and immune modulatory therapy is now approved for clinical use. However, while the majority of studies on the inflammatory tumour microenvironment have focused on the cellular immune response, in particular the prognostic and predictive role of various T cell infiltrates, the role of the humoral immune response in this context has long been overlooked. This study aimed to investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in epithelial ovarian cancer (EOC).

Methods

Immunohistochemical expression of immunoglobulin kappa C (IGKC), CD20 and CD138 was analysed in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian tubes (n = 38) and omental metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of immune-cell specific IGKC, CD20 and CD138 expression on overall survival and ovarian cancer-specific survival.

Results

High IGKC expression correlated significantly with expression of CD20 (p = 0.001) and CD138 (p = 0.035). Expression of IGKC as well as CD138 was significantly higher in primary tumours than in fallopian tubes (p = 0.004 and p = 0.001, respectively). High CD20 and CD138 expression correlated significantly with high tumour grade (p = 0.032 and p = 0.030, respectively). CD20 and IGKC expression was not prognostic but univariable Cox regression analysis revealed high CD138 expression to correlate with a significantly reduced overall survival (HR = 2.20; 95 % CI 1.34–3.55; p–0.001) as well as ovarian cancer-specific survival (HR = 1.95; 95 % CI 1.28–2.98; p = 0.002). The prognostic impact was independent of established clinical parameters (age, grade, clinical stage) as shown in multivariable analysis (HR = 2.28; 95 % CI 1.39–3.75; p = 0.001).

Conclusions

In conclusion, our results demonstrate that plasma cell infiltration in epithelial ovarian cancer has a significant impact on tumour progression and prognosis. The important role of the humoral immune system merits further study and may be harnessed as immune modulatory strategies in cancer therapy.
Appendix
Available only for authorised users
Literature
1.
2.
3.
4.
5.
Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012;30(17):2046–54.CrossRefPubMed
6.
Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.CrossRefPubMed
7.
Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.CrossRefPubMed
8.
Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008;68(13):5405–13.CrossRefPubMed
9.
Lohr M, Edlund K, Botling J, Hammad S, Hellwig B, Othman A, et al. The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer. Cancer Lett. 2013;333(2):222–8.CrossRefPubMed
10.
Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, et al. A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors. Clin Cancer Res. 2012;18(9):2695–703.CrossRefPubMed
11.
Matsuzaki H, Kobayashi H, Yagyu T, Wakahara K, Kondo T, Kurita N, et al. Reduced syndecan-1 expression stimulates heparin-binding growth factor-mediated invasion in ovarian cancer cells in a urokinase-independent mechanism. Oncol Rep. 2005;14(2):449–57.PubMed
12.
Kusumoto T, Kodama J, Seki N, Nakamura K, Hongo A, Hiramatsu Y. Clinical significance of syndecan-1 and versican expression in human epithelial ovarian cancer. Oncol Rep. 2010;23(4):917–25.PubMed
13.
Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, et al. Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer. Clin Cancer Res. 2004;10(15):5178–86.CrossRefPubMed
14.
Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, et al. CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res. 2012;18(12):3281–92.CrossRefPubMed
15.
Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, et al. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One. 2009;4(7):e6412.CrossRefPubMedPubMedCentral
16.
Berntsson J, Lundgren S, Nodin B, Uhlen M, Gaber A, Jirstrom K. Expression and prognostic significance of the polymeric immunoglobulin receptor in epithelial ovarian cancer. J Ovarian Res. 2014;7(1):26. 2215-7-26.CrossRefPubMedPubMedCentral
17.
Berglund G, Elmstahl S, Janzon L, Larsson SA. The Malmo Diet and Cancer Study. Design and feasibility. J Intern Med. 1993;233(1):45–51.CrossRefPubMed
18.
Nilsson PM, Nilsson JA, Berglund G. Population-attributable risk of coronary heart disease risk factors during long-term follow-up: the Malmo Preventive Project. J Intern Med. 2006;260(2):134–41.CrossRefPubMed
19.
Nodin B, Hedner C, Uhlen M, Jirstrom K. Expression of the global regulator SATB1 is an independent factor of poor prognosis in high grade epithelial ovarian cancer. J Ovarian Res. 2012;5(1):24.CrossRefPubMedPubMedCentral
20.
Ehlen A, Brennan DJ, Nodin B, O'Connor DP, Eberhard J, Alvarado-Kristensson M, et al. Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer. J Transl Med. 2010;8:78.CrossRefPubMedPubMedCentral
21.
Ehlen A, Nodin B, Rexhepaj E, Brandstedt J, Uhlen M, Alvarado-Kristensson M, et al. RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Transl Oncol. 2011;4(4):212–21.CrossRefPubMedPubMedCentral
22.
Nodin B, Fridberg M, Uhlen M, Jirstrom K. Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer. J Ovarian Res. 2012;5(1):6.CrossRefPubMedPubMedCentral
23.
Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagn Pathol. 2013;8:106.CrossRefPubMedPubMedCentral
24.
Mantovani A, Romero P, Palucka AK, Marincola FM. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet. 2008;371(9614):771–83.CrossRefPubMed
25.
Nelson BH. The impact of T-cell immunity on ovarian cancer outcomes. Immunol Rev. 2008;222:101–16.CrossRefPubMed
26.
Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–13.CrossRefPubMed
27.
Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):192–8.CrossRefPubMedPubMedCentral
28.
Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104(9):3360–5.CrossRefPubMedPubMedCentral
29.
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. 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. 2005;102(51):18538–43.CrossRefPubMedPubMedCentral
30.
Mohammed ZM, Going JJ, Edwards J, Elsberger B, McMillan DC. The relationship between lymphocyte subsets and clinico-pathological determinants of survival in patients with primary operable invasive ductal breast cancer. Br J Cancer. 2013;109(6):1676–84.CrossRefPubMedPubMedCentral
31.
Ness RB, Cottreau C. Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst. 1999;91(17):1459–67.CrossRefPubMed
32.
DeNardo DG, Coussens LM. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 2007;9(4):212.CrossRefPubMedPubMedCentral
33.
Affara NI, Ruffell B, Medler TR, Gunderson AJ, Johansson M, Bornstein S, et al. B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell. 2014;25(6):809–21.CrossRefPubMedPubMedCentral
34.
Chapoval AI, Fuller JA, Kremlev SG, Kamdar SJ, Evans R. Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells. J Immunol. 1998;161(12):6977–84.PubMed
35.
Nguyen TL, Grizzle WE, Zhang K, Hameed O, Siegal GP, Wei S. Syndecan-1 overexpression is associated with nonluminal subtypes and poor prognosis in advanced breast cancer. Am J Clin Pathol. 2013;140(4):468–74.CrossRefPubMed
36.
Juuti A, Nordling S, Lundin J, Louhimo J, Haglund C. Syndecan-1 expression--a novel prognostic marker in pancreatic cancer. Oncology. 2005;68(2–3):97–106.CrossRefPubMed
37.
Bodoor K, Matalka I, Hayajneh R, Haddad Y, Gharaibeh W. Evaluation of BCL-6, CD10, CD138 and MUM-1 expression in diffuse large B-cell lymphoma patients: CD138 is a marker of poor prognosis. Asian Pac J Cancer Prev. 2012;13(7):3037–46.CrossRefPubMed
38.
Rousseau C, Ruellan AL, Bernardeau K, Kraeber-Bodere F, Gouard S, Loussouarn D, et al. Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors. EJNMMI Res. 2011;1(1):20.CrossRefPubMedPubMedCentral
39.
40.
Wang X, Zuo D, Chen Y, Li W, Liu R, He Y, et al. Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer. Br J Cancer. 2014;111(10):1965–76.CrossRefPubMedPubMedCentral
41.
Schmidt M, Micke P, Gehrmann M, Hengstler JG. Immunoglobulin kappa chain as an immunologic biomarker of prognosis and chemotherapy response in solid tumors. Oncoimmunology. 2012;1(7):1156–8.CrossRefPubMedPubMedCentral
42.
Kroeger DR, Milne K, Nelson BH. Tumor infiltrating plasma cells are associated with tertiary lymphoid structures, cytolytic T cell responses, and superior prognosis in ovarian cancer. Clin Cancer Res. 2016
43.
Ai J, Tang Q, Wu Y, Xu Y, Feng T, Zhou R, et al. The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma. J Natl Cancer Inst. 2011;103(22):1696–712.CrossRefPubMedPubMedCentral
44.
Rossel M, Billerey C, Bittard H, Ksiazek P, Alber D, Revillard JP, et al. Alterations in polymeric immunoglobulin receptor expression and secretory component levels in bladder carcinoma. Urol Res. 1991;19(6):361–6.CrossRefPubMed
45.
Fristedt R, Gaber A, Hedner C, Nodin B, Uhlen M, Eberhard J, et al. Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma. J Transl Med. 2014;12(1):83. 5876-12-83.CrossRefPubMedPubMedCentral
46.
Fristedt R, Elebro J, Gaber A, Jonsson L, Heby M, Yudina Y, et al. Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis. PLoS One. 2014;9(11):e112728.CrossRefPubMedPubMedCentral
Metadata
Title
Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer
Authors
Sebastian Lundgren
Jonna Berntsson
Björn Nodin
Patrick Micke
Karin Jirström
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0232-0

Other articles of this Issue 1/2016

Journal of Ovarian Research 1/2016 Go to the issue

Research

SNAP23 promotes the malignant process of ovarian cancer

Research

Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation

Review

Used protocols for isolation and propagation of ovarian stem cells, different cells with different traits

Research

Prophylactic salpingo-oophorectomy in BRCA1 mutation carriers and postoperative incidence of peritoneal and breast cancers

Research

The effect of FSH and activin A on Akt and MAPK1/3 phosphorylation in cultured bovine ovarian cortical strips

Research

Fertility-sparing surgery for young patients with borderline ovarian tumors (BOTs): single institution experience