Profiling the immune landscape in mucinous ovarian carcinoma
- Author(s)
- Meagher, NS; Hamilton, P; Milne, K; Thornton, S; Harris, B; Weir, A; Alsop, J; Bisinoto, C; Brenton, JD; Brooks-Wilson, A; Chiu, DS; Cushing-Haugen, KL; Fereday, S; Garsed, DW; Gayther, SA; Gentry-Maharaj, A; Gilks, B; Jimenez-Linan, M; Kennedy, CJ; Le, ND; Piskorz, AM; Riggan, MJ; Shah, M; Singh, N; Talhouk, A; Widschwendter, M; Bowtell, DDL; Candido Dos Reis, FJ; Cook, LS; Fortner, RT; García, MJ; Harris, HR; Huntsman, DG; Karnezis, AN; Köbel, M; Menon, U; Pharoah, PDP; Doherty, JA; Anglesio, MS; Pike, MC; Pearce, CL; Friedlander, ML; DeFazio, A; Nelson, BH; Ramus, SJ;
- Journal Title
- Gynecologic Oncology
- Abstract
- OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.
- Publisher
- Elsevier
- Keywords
- Humans; Female; *B7-H1 Antigen/genetics; Carcinoma, Ovarian Epithelial/pathology; *Ovarian Neoplasms/drug therapy; CD8-Positive T-Lymphocytes; Forkhead Transcription Factors/therapeutic use; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment; Immune infiltrate; Mucinous ovarian carcinoma; Rare histotype
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 36368129
- Publisher's Version
- https://doi.org/10.1016/j.ygyno.2022.10.022
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ygyno.2022.10.022 - Terms of Use/Rights Notice
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Creation Date: 2024-01-16 09:40:56
Last Modified: 2024-01-16 09:46:07