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

Lundgren, Sebastian LU ; Berntsson, Jonna LU ; Nodin, Björn LU ; Micke, Patrick and Jirström, Karin LU (2016) In Journal of Ovarian Research 9(1).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Ovarian Research
volume
9
issue
1
publisher
BioMed Central
external identifiers
  • WOS:000373672200001
  • Scopus:84964462289
ISSN
1757-2215
DOI
10.1186/s13048-016-0232-0
language
English
LU publication?
yes
id
67dae16c-ac0e-4eeb-aeb6-8300b7db36c9
date added to LUP
2016-04-28 13:48:47
date last changed
2016-10-30 04:46:54
@misc{67dae16c-ac0e-4eeb-aeb6-8300b7db36c9,
  abstract     = {<p>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).</p><p>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.</p><p>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).</p><p>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.</p>},
  author       = {Lundgren, Sebastian and Berntsson, Jonna and Nodin, Björn and Micke, Patrick and Jirström, Karin},
  issn         = {1757-2215},
  language     = {eng},
  number       = {1},
  publisher    = {ARRAY(0xa223960)},
  series       = {Journal of Ovarian Research},
  title        = {Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer},
  url          = {http://dx.doi.org/10.1186/s13048-016-0232-0},
  volume       = {9},
  year         = {2016},
}