Profiling the immune landscape in mucinous ovarian carcinoma

Meagher, N.S.; Hamilton, P.; Milne, K.; Thornton, S.; Harris, B.; Weir, A.; Alsop, J.; Bisinoto, C.; Brenton, J.D.; Brooks-Wilson, A.; Chiu, D.S.; Cushing-Haugen, K.L.; Fereday, S.; Garsed, D.W.; Gayther, S.A.; Gentry-Maharaj, A.; Gilks, B.; Jimenez-Linan, M.; Kennedy, C.J.; Le, N.D.; Piskorz, A.M.; Riggan, M.J.; Shah, M.; Singh, N.; Talhouk, A.; Widschwendter, M.; Bowtell, D.D.L.; Candido Dos Reis, F.J.; Cook, L.S.; Fortner, R.ée.T.; García, M.ía.J.; Harris, H.R.; Huntsman, D.G.; Karnezis, A; Meagher, N.S; Hamilton, P; Milne, K; Thornton, S; Harris, B; Weir, A; Alsop, J; Bisinoto, C; Brenton, J.D; Brooks-Wilson, A; Chiu, D.S; Cushing-Haugen, K.L; Fereday, S; Garsed, D.W; Gayther, S.A; Gentry-Maharaj, A; Gilks, B; Jimenez-Linan, M; Kennedy, C.J; Le, N.D

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Profiling the immune landscape in mucinous ovarian carcinoma

Meagher, N.S.; Hamilton, P.; Milne, K.; Thornton, S.; Harris, B.; Weir, A.; Alsop, J.; Bisinoto, C.; Brenton, J.D.; Brooks-Wilson, A.; Chiu, D.S.; Cushing-Haugen, K.L.; Fereday, S.; Garsed, D.W.; Gayther, S.A.; Gentry-Maharaj, A.; Gilks, B.; Jimenez-Linan, M.; Kennedy, C.J.; Le, N.D.; Piskorz, A.M.; Riggan, M.J.; Shah, M.; Singh, N.; Talhouk, A.; Widschwendter, M.; Bowtell, D.D.L.; Candido Dos Reis, F.J.; Cook, L.S.; Fortner, R.ée.T.; García, M.ía.J.; Harris, H.R.; Huntsman, D.G.; Karnezis, A

Gynecologic Oncology 168: 23-31

2023

ISSN/ISBN: 1095-6859

PMID: 36368129

Accession: 080653818

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Summary

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. 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. 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. In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.

Profiling the immune landscape in mucinous ovarian carcinoma

Gynecologic Oncology 168: 23-31

2023

Full-Text Article emailed within 1 workday

Summary

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