Abstract
Purpose: Ovarian cancer is one of the first human cancers for which in situ immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required.Experimental Design: From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score. The relationships between immune score, tumor-infiltrating immune cells, cancer genotypes, and their impact on patient outcome were characterized.Results: Loss of chemokine and IFNγ pathway genes is frequent in ovarian cancer and is significantly associated with low immune score and poor outcome. Chemotherapy can increase the immune score of tumors by inducing the expression of IFNγ inducible chemokines. High immune score is significantly associated with BRCA1/2 mutation status and the response to chemotherapy. Multivariate analysis revealed that immune score is a strong predictor of patient survival and the response to immunotherapy.Conclusions: Our results reveal the drivers of the immune repertoire of advanced ovarian cancer and demonstrate the importance of immune score as an independent prognostic signature and a potent indicator of intratumoral immune status. Clin Cancer Res; 24(15); 3560-71. ©2018 AACR.
Highlights
Since the first piece of evidence for the infiltration of cytotoxic T cells in epithelial ovarian cancer (EOC) was reported in 1991 [1], many studies have confirmed a spontaneous antitumor immune response in EOC patients [2]
Loss of chemokine and IFNg pathway genes is frequent in ovarian cancer and is significantly associated with low immune score and poor outcome
Chemotherapy can increase the immune score of tumors by inducing the expression of IFNg inducible chemokines
Summary
Since the first piece of evidence for the infiltration of cytotoxic T cells in epithelial ovarian cancer (EOC) was reported in 1991 [1], many studies have confirmed a spontaneous antitumor immune response in EOC patients [2]. EOC is one of the first human cancers for which tumor-infiltrating lymphocytes (TIL) was found to be associated with improved patient survival and delayed recurrence of disease [3]. Recent studies further confirmed the prognostic value of TILs using multiple EOC cohorts [4]. In light of the promising effect of immunotherapy in the initial studies of EOC [5, 6], especially in patients that are resistant to the conventional therapy, ongoing clinical trials are designed to evaluate the effect of immune-checkpoint inhibitors in EOC patients [7]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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