Rare mucinous ovarian carcinoma (MOC) patients have a dismal prognosis, as this histotype of ovarian cancer seldom responds to regular chemotherapy. In addition, the immunological landscape of MOC is poorly understood, making it difficult to say if immune checkpoint inhibitors should be used for any individuals. Tissue microarrays were subjected to multicolor immunohistochemistry (IHC) and immunofluorescence (IF) in a cohort of 126 patients with MOC.
Epithelial and stromal cell densities were determined and compared with clinical variables 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+), Total survival was analyzed using both univariate and multivariate Cox Proportional Hazards models. Patients who showed similar patterns of immune cell infiltration were clustered together using unsupervised k-means analysis. The stroma had a greater average density of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs than the epithelium. Epithelial infiltration of PD-L1- and PD-L1+ macrophages was higher in Stage III/IV MOC tumors than in Stage I/II MOC tumors (P = 0.004 and P = 0.014, respectively).
Under univariate analysis, patients with a high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages fared worse, while those with a high epithelial density of CD79a + plasma cells fared better. According to cluster analysis, the vast majority of MOC (86%) displayed an immune-depleted (cold) phenotype, with just a subset being termed immunological inflamed (hot) based on T cell and PD-L1 infiltrates. In conclusion, MOCs are generally “cool” immunologically, which means they may not respond well to standard immunotherapies.
Source: www.sciencedirect.com/science/article/pii/S0090825822018996
