Abstract
Background: Increasing evidence supporting that immune infiltration of tumors is associated with prognosis. Here, we sought to access the relevance of cellular composition of the immune infiltrate to survival after platinum-based chemotherapy among high grade serous ovarian cancer patients, and evaluate these effects by molecular subtypes. Methods: We searched for publicly available database and identified 13 studies with >2,000 patients. We estimated the proportions of 22 immune cell subsets using a proposed computational approach (CIBERSORT), then investigated associations between each cell type and progression-free survival (PFS) and overall survival (OS), with cellular proportions be modelled as quartiles. Findings: A higher fraction of M0 macrophages (hazard ratio [HR] = 0.86, 95% CI=0.80 to 0.92) and activated natural killer (NK) cells (HR = 0.89, 95% CI=0.84 to 0.96) emerged as the most closely associated with favorable OS. Monocytes was associated with poor OS (HR = 1.11, 95% CI=1.04 to 1.18) and PFS (HR = 1.11, 95% CI=1.04 to 1.19;), as well as neutrophils (HR = 1.10, 95% CI =1.03 to 1.17 for OS; HR = 1.12, 95% CI=1.04 to 1.21 for PFS. Among immunoreactive tumors, M0 macrophages, activated NK and CD8+ T cells were conferred improved OS, while M2 macrophages and monocytes were conferred worse OS. T cell gamma delta conferred poor PFS in proliferative subtype. Four subgroups of tumors with distinct survival patterns were identified using immune cell proportions with unsupervised clustering. Interpretation: Further investigations of the quantitative of cellular immune infiltrations in tumors may make contributions for therapeutic advances. Funding Statement: This study was supported by the National Scientific Foundation of China (No. 31801121, 81522048 and 81573511), Scientific Foundation of Xiang Ya hospital (2016Q04) and the National Key Research and Development Program (No. 2016YFC0905000, 2016YFC0905001). Declaration of Interests: The authors stated: None. Ethics Approval Statement: This study has been approved by the Institute of Clinical Pharmacology, Central South University.
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