High RIG‐I expression in ovarian cancer associates with an immune‐escape signature and poor clinical outcome

Abstract

Ovarian cancer (OC) is the most lethal gynecological malignancy, with platinum‐based chemotherapy remaining the mainstay for adjuvant treatment after surgery. The lack of indication for immunotherapy may at least in part result from the lack of suitable biomarkers allowing stratification of potentially responding patients. In this monocentric study of 141 cases with OC, we used real‐time quantitative PCR to assess the expression of retinoic acid‐inducible gene‐I (RIG‐I) in primary tumor and healthy ovarian control tissues. RIG‐I expression was correlated to various clinicopathological characteristics as well as to a set of molecular and immunological markers. The prognostic significance of RIG‐I expression was queried in univariate and multivariate analyses and validated in an independent cohort. RIG‐I was overexpressed in the cancerous ovary and correlated with a higher tumor grade. The more aggressive Type‐II cancers and cancers with inactivating p53 mutations exhibited higher RIG‐I expression. RIG‐I levels were also elevated in cancers that recurred after remission or were platinum‐refractory. Survival analyses disclosed RIG‐I as an independent marker of poor outcome in OC. Continuative analyses revealed the molecular and immunological correlates of RIG‐I expression in the tumor microenvironment, including interferon production and a distinct immune‐regulatory signature involving checkpoint molecules (PD‐L1/PD‐1), the RNA‐editing enzyme ADAR1 and the regulatory T cell‐specific transcription factor FoxP3. We conclude that high RIG‐I expression associates with poor outcome in OC, which is explainable by local immunosuppression in the tumor bed. RIG‐I expression may inform checkpoint blockade and/or RIG‐I agonistic targeting in a subset of high‐risk OC patients.

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

“…The most likely reason for this result was a multicollinearity problem. With regard to this phenomenon, similar results were also found in numerous tumor studies (69)(70)(71). Next, the prediction power of each of the two lncRNAs was estimated on the basis of the ROC curve, and the results revealed that lnc-8996 and lnc-4265 had better diagnostic prediction power (AUC equals 0.867 and 0.815, respectively).…”

NanoString technology distinguishes anti‐TIF‐1γ+ from anti‐Mi‐2+ dermatomyositis patients

“…Immunohistochemically, the expression of RIG-1 was found on the sarcolemma of muscle fibers in the perifascicular area and on single immune cells in both subgroups (anti-Mi-2 + , anti-TIF-1γ + ). DDX58/RIG-1 was shown to be directly involved in virus recognition and interferon production (47,(65)(66)(67). Nevertheless, it has been shown that increased RIG-1 expression may be involved in limiting innate immune response and supporting tumor growth (67).…”

Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

“…Retinoic acid Inducible Gene 1 (RIG-I) is a cytosolic RNA receptor ubiquitously expressed in most human body cells and is known for its major role in antiviral immune defense by inducing pyroptosis. RIG-I is also expressed in cancer cells, acting pro-inflammatory by expressing INF I and other cytokines [ 130 ]. In preclinical models, systemically applied RIG-I agonists were able to inhibit tumor growth via induction of immunogenic cancer cell death [ 131 – 133 ].…”