Profiling the immune landscape in mucinous ovarian carcinoma.

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.

Authors:

NS Meagher, P Hamilton, K Milne, S Thornton, B Harris, A Weir, J Alsop, C Bisinoto, JD Brenton, A Brooks-Wilson, DS Chiu, KL Cushing-Haugen, S Fereday, DW Garsed, SA Gayther, A Gentry-Maharaj, B Gilks, M Jimenez-Linan, CJ Kennedy, ND Le, AM Piskorz, MJ Riggan, M Shah, N Singh, A Talhouk, M Widschwendter, DDL Bowtell, FJ Candido Dos Reis, LS Cook, RT Fortner, MJ García, HR Harris, DG Huntsman, AN Karnezis, M Köbel, U Menon, PDP Pharoah, JA Doherty, MS Anglesio, MC Pike, CL Pearce, ML Friedlander, A DeFazio, BH Nelson, SJ Ramus

Journal:

Gynecol Oncol

Citation info:

168:23-31

Publication date:

1st Jan 2023

Full text

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