Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer - PubMed (original) (raw)
. 2016 Jun 15;22(12):3005-15.
doi: 10.1158/1078-0432.CCR-15-2762. Epub 2016 Jan 13.
Affiliations
- PMID: 26763251
- DOI: 10.1158/1078-0432.CCR-15-2762
Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer
David R Kroeger et al. Clin Cancer Res. 2016.
Abstract
Purpose: CD8(+) tumor-infiltrating lymphocytes (TIL) are key mediators of antitumor immunity and are strongly associated with survival in virtually all solid tumors. However, the prognostic effect of CD8(+) TIL is markedly higher in the presence of CD20(+) B cells, suggesting that cooperative interactions between these lymphocyte subsets lead to more potent antitumor immunity.
Experimental design: We assessed the colocalization patterns, phenotypes, and gene expression profiles of tumor-associated T- and B-lineage cells in high-grade serous ovarian cancer (HGSC) by multicolor IHC, flow cytometry, and bioinformatic analysis of gene expression data from The Cancer Genome Atlas.
Results: T cells and B cells colocalized in four types of lymphoid aggregate, ranging from small, diffuse clusters to large, well-organized tertiary lymphoid structures (TLS) resembling activated lymph nodes. TLS were frequently surrounded by dense infiltrates of plasma cells (PC), which comprised up to 90% of tumor stroma. PCs expressed mature, oligoclonal IgG transcripts, indicative of antigen-specific responses. PCs were associated with the highest levels of CD8(+), CD4(+), and CD20(+) TIL, as well as numerous cytotoxicity-related gene products. CD8(+) TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. PCs were independent of mutation load, BRCA1/2 status, and differentiation antigens but positively associated with cancer-testis antigens.
Conclusions: PCs are associated with the most robust, prognostically favorable CD8(+) TIL responses in HGSC. We propose that TLS facilitate coordinated antitumor responses involving the combined actions of cytolytic T cells and antibody-producing PCs. Clin Cancer Res; 22(12); 3005-15. ©2016 AACR.
©2016 American Association for Cancer Research.
Similar articles
- CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer.
Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH. Nielsen JS, et al. Clin Cancer Res. 2012 Jun 15;18(12):3281-92. doi: 10.1158/1078-0432.CCR-12-0234. Epub 2012 May 2. Clin Cancer Res. 2012. PMID: 22553348 - PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer.
Webb JR, Milne K, Kroeger DR, Nelson BH. Webb JR, et al. Gynecol Oncol. 2016 May;141(2):293-302. doi: 10.1016/j.ygyno.2016.03.008. Epub 2016 Mar 16. Gynecol Oncol. 2016. PMID: 26972336 - Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy.
Lo CS, Sanii S, Kroeger DR, Milne K, Talhouk A, Chiu DS, Rahimi K, Shaw PA, Clarke BA, Nelson BH. Lo CS, et al. Clin Cancer Res. 2017 Feb 15;23(4):925-934. doi: 10.1158/1078-0432.CCR-16-1433. Epub 2016 Sep 6. Clin Cancer Res. 2017. PMID: 27601594 - Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma.
Maibach F, Sadozai H, Seyed Jafari SM, Hunger RE, Schenk M. Maibach F, et al. Front Immunol. 2020 Sep 10;11:2105. doi: 10.3389/fimmu.2020.02105. eCollection 2020. Front Immunol. 2020. PMID: 33013886 Free PMC article. Review. - Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer.
Wouters MCA, Nelson BH. Wouters MCA, et al. Clin Cancer Res. 2018 Dec 15;24(24):6125-6135. doi: 10.1158/1078-0432.CCR-18-1481. Epub 2018 Jul 26. Clin Cancer Res. 2018. PMID: 30049748 Review.
Cited by
- Exploring the impact of tertiary lymphoid structures maturity in NSCLC: insights from TLS scoring.
Berthe J, Poudel P, Segerer FJ, Jennings EC, Ng F, Surace M, Andoni A, Testori M, Saraiya M, Vuko M, Hessel H, Heininen-Brown M, Blando J, Jones EV, Willis SE, Galon J, van de Ven R, de Gruijl TD, Angell HK. Berthe J, et al. Front Immunol. 2024 Sep 20;15:1422206. doi: 10.3389/fimmu.2024.1422206. eCollection 2024. Front Immunol. 2024. PMID: 39376565 Free PMC article. - Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors.
Lingo JJ, Voigt E, Quelle DE. Lingo JJ, et al. Oncotarget. 2024 Sep 30;15:638-643. doi: 10.18632/oncotarget.28650. Oncotarget. 2024. PMID: 39347707 Free PMC article. Review. - Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma.
Lacinski RA, Dziadowicz SA, Melemai VK, Fitzpatrick B, Pisquiy JJ, Heim T, Lohse I, Schoedel KE, Llosa NJ, Weiss KR, Lindsey BA. Lacinski RA, et al. Bone Res. 2024 Sep 27;12(1):55. doi: 10.1038/s41413-024-00359-z. Bone Res. 2024. PMID: 39333065 Free PMC article. - Tertiary lymphoid structures in anticancer immunity.
Teillaud JL, Houel A, Panouillot M, Riffard C, Dieu-Nosjean MC. Teillaud JL, et al. Nat Rev Cancer. 2024 Sep;24(9):629-646. doi: 10.1038/s41568-024-00728-0. Epub 2024 Aug 8. Nat Rev Cancer. 2024. PMID: 39117919 Review. - Characterization of latently infected EBV+ antibody-secreting B cells isolated from ovarian tumors and malignant ascites.
Zhang L, Strange M, Elishaev E, Zaidi S, Modugno F, Radolec M, Edwards RP, Finn OJ, Vlad AM. Zhang L, et al. Front Immunol. 2024 Jul 17;15:1379175. doi: 10.3389/fimmu.2024.1379175. eCollection 2024. Front Immunol. 2024. PMID: 39086481 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous