The Immune Subtype Contributes to Distinct Overall Survival for Ovarian Cancer Patients With Platinum-Based Adjuvant Therapy

Abstract

ObjectiveNowadays, platinum-based therapy has been widely used as the first-line therapy of ovarian cancer. However, the effect of the tumor microenvironment on platinum-based therapy remains unclear. In this study, we aim to investigate the relationship between immune microenvironment subtypes and the prognosis of platinum-based therapy in ovarian cancer.MethodsWe integrated 565 ovarian cancer samples from two datasets and obtained the immune subtypes (ISs) by consistent clustering of 1190 immune-related gene expressions. The proportional hazards regression model was used to assess the relationship between ISs and the prognosis of platinum-based adjuvant therapy including progression-free survival (PFS) and overall survival (OS). The prognostic contribution of ISs was validated in three additional cohorts. Non-parametric tests were used to assess genomic characteristics, the proportion of immune cells, and immune-related signature differences among ISs.ResultsWe identified and validated five ISs associated with different clinical outcomes of the platinum-based adjuvant therapy in ovarian cancer patients. These differences were only found in OS rather than PFS. An immune subtype had the worst OS. Those patients mainly derived from the mesenchymal subtype had the lowest tumor purity with a high leukocyte fraction as well as stromal fraction and had the highest TGF-β response signaling. By contrast, an immune subtype characterized by immunoreactive status with the highest CD8+T cell infiltration and elevated IFN-γ response signaling had the best prognosis. Other subtypes with more diverse immunologic features such as lowest macrophage regulation signaling showed intermediate prognoses. Notably, the contribution of ISs to OS was independent of the clinical response to platinum-based drugs.ConclusionOur analysis revealed the association between different immune characteristics and platinum-based adjuvant therapy, indicating the combination of ISs and chemotherapy could optimize the treatment strategy of OC patients.

A methylation- and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance

“…Furthermore, CD8 + T cells are known to signify a favorable clinical outcome in a variety of tumors, including OC [ 53 ]. Therefore, combined with previous studies, we found that CD8 + T cells can predict the prognosis of OC patients [ 41 ]. The study also showed that the risk score was negatively correlated with the proportions of resting immune cells but positively associated with immunosuppressive cells, indicating that patients with low-risk scores were immunologically resting, while those with high-risk scores represented an immunosuppressive tumor microenvironment.…”

“…Multiple studies have reported an association between the extent of infiltrating immune cells and the prognosis of OC [ 41 , 42 ]. To analyze the connection between the immune prognostic risk model and immune cell infiltration, the CIBERSORT algorithm was employed to investigate the expression of 22 subpopulations of immune cells in OC tissues.…”

The role of interferons in ovarian cancer progression: Hinderer or promoter?

“…Tyrosine kinase 2 (TYK2), an enzyme that plays a key role in IFN-I signaling, was reduced in abundance in CAOV3 CBPR cells (89). This conclusion was similarly validated by clinical data showing that patients with high IFN-g in the immune microenvironment had a better prognosis in platinum-treated patients (90). Furthermore, it has been shown that cancer cells pretreated by IFN-b were more likely to expose calreticulin and aided immunogenic cell death (ICD) when receiving platinum treatment through the IRF1 pathway (91).…”

High Tumor-Infiltrating Lymphocyte Count Is Associated with Distinct Gene Expression Profile and Longer Patient Survival in Advanced Ovarian Cancer

“…Early- and advanced-stage tumors were reported to have different CD45RA + tumor-infiltrating leukocytes (50% vs. 10.5%, respectively) [ 45 ]. Patients from a mesenchymal subtype (derived from immune gene expression subtyping in ovarian cancer) had the lowest tumor purity, a high leukocyte fraction, and a stromal fraction with the highest TGF-β response [ 47 ]. Furthermore, in patients with brain metastasis, it has been found that both the primary and brain metastasis samples contained approximately the same amount of CD45RO + and CD8 + tumor-infiltrating immune cells [ 48 ], similar to that of the study investigating the omental metastasis samples detailed above [ 27 ].…”