Abstract
BackgroundThe 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).MethodsImmunohistochemical 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.ResultsHigh 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).ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0232-0) contains supplementary material, which is available to authorized users.
Highlights
The critical role of the immune system in controlling cancer progression has become evident and immune modulatory therapy is approved for clinical use
We aimed to investigate if these markers correlate with expression of the polymeric immunoglobulin receptor (PIGR), which has previously been described as an indicator of a less aggressive tumour phenotype and improved survival in epithelial ovarian cancer (EOC) [16]
The expression of the three biomarkers did not differ significantly between primary tumours and metastases, ; both immunoglobulin kappa C (IGKC) and CD138 expression was found to be significantly higher in primary tumours than in fallopian tubes (p = 0.004 and p = 0.001, respectively) (Fig. 2)
Summary
The critical role of the immune system in controlling cancer progression has become evident and immune modulatory therapy is approved for clinical use. 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. Inflammation caused by cancer and specific immune cell infiltrates have demonstrated tumorigenic properties [3]. The majority of studies concerning the role of the immune system in cancer have focused on the cellular response. High infiltration of specific T-lymphocytes has been associated with favourable clinical outcome in many tumour types and an immune index has been suggested to outperform classical prognostic parameters in colon cancer [7]. The humoral anti-tumour response, has been far less investigated
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