Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma

Abstract

Background In colorectal and breast cancer, the density and localisation of immune infiltrates provides strong prognostic information. We asked whether similar automated quantitation and combined analysis of immune infiltrates could refine prognostic information in high-grade serous ovarian carcinoma (HGSOC) and tested associations between patterns of immune response and genomic driver alterations. Methods Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO⁺, CD8⁺ and CD68⁺ cells was automatically quantified from images of 332 HGSOC patient tissue microarray cores. Results Epithelial CD8 [p = 0.027, hazard ratio (HR) = 0.83], stromal CD68 (p = 3 × 10⁻⁴, HR = 0.44) and stromal CD45RO (p = 7 × 10⁻⁴, HR = 0.76) were positively associated with survival and remained so when averaged across the tumour and stromal compartments. Using principal component analysis, we identified optimised multiparameter survival models combining information from all immune markers (p = 0.016, HR = 0.88). There was no significant association between PTEN expression, type of TP53 mutation or presence of BRCA1/BRCA2 mutations and immune infiltrate densities or principal components. Conclusions Combining measures of immune infiltration provided improved survival modelling and evidence for the multiple effects of different immune factors on survival. The presence of stromal CD68⁺ and CD45RO⁺ populations was associated with survival, underscoring the benefits evaluating stromal immune populations may bring for prognostic immunoscores in HGSOC.