Abstract

Abstract Objective: Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates that reflect lymphoid neogenesis mainly through CXCL13 and develop under chronic inflammation. Recently TLS have been detected in several types of cancers; however, there are few reports about TLS in ovarian cancer. We investigated the clinical significance of TLS in ovarian cancer. Methods: 28 patients who were diagnosed with high-grade serous ovarian cancer and treated surgically in our hospital were selected from microarray dataset (KOV-75; GSE39204/55512). We evaluated TLS, tumor-infiltrating lymphocyte (TIL) subsets (CD4+ T cell, CD8+ T cell, CD20+ B cell, CD38+ plasma cell), and the correlation between expression of CXCL13 and TIL subsets by immunohistochemical staining. We analyzed the correlation between gene expression of CXCL13 and the survival time of the patients (pts) by using KOV-75 and the cancer genome atlas (TCGA) datasets. Results: Immunohistochemical staining revealed that TLS were detected in 64% (18 pts) of ovarian cancer patients, and the numbers of tumor-infiltrating CD8+ T cells, CD20+ B cells and CD38+ plasma cells were significantly higher in cases with TLS (p<0.05). The numbers of tumor-infiltrating CD4+ T cells, CD8+ T cells, CD20+ B cells and CD38+ plasma cells were significantly higher in the CXCL13-high tumor than in the CXCL13-low tumor (p<0.001). In the group with high intratumoral infiltration of CD8 T cells and plasma cells, progression-free survival and overall survival were both significantly extended (p<0.05, respectively). In microarray analyses of KOV-75 and TCGA, high CXCL13 gene expression correlated significantly with both favorable progression-free survival and overall survival (p<0.05, respectively). Conclusion: CXCL13 contributes to better prognosis in ovarian cancer patients by inducing TLS and various subsets of TIL. Induction of CXCL13 might be a new therapeutic target for ovarian cancer patients. Citation Format: Masayo Ukita, Junzo Hamanishi, Tsukasa Baba, Ryusuke Murakami, Kaoru Abiko, Masaki Mandai. Clinical significance of tertiary lymphoid structures (TLS) and tumor-infiltrating plasma cells in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1021.

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