scholarly journals A Pan-cancer Analysis of the Prognostic and Immunological Role of PPP1R14A

2021 ◽  
Author(s):  
JiaJie Lu ◽  
Rihong Huang ◽  
Haojian Wang ◽  
Yuecheng Peng ◽  
Yongyang Fan ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Cancer Survival ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Poor Overall Survival ◽  
Carcinogenic Effect ◽  
Genetic Changes ◽  
Pan Cancer

Abstract BackgroundDespite emerging evidence revealed the remarkable roles of Protein Phosphatase 1 Regulatory Inhibitor Subunit 14A (PPP1R14A) in cancer tumorigenesis and progression, no pan-cancer analysis is available. Our research, for the first time, comprehensively investigated the potential carcinogenic mechanism of PPP1R14A across 33 tumors using bioinformatic techniques. MethodsTCGA datasets and the CPTAC datasets embedded in UALCAN were first applied to study the differential expression of PPP1R14A in various cancer types at the transcription and protein levels, respectively. Besides, we also conducted relevant prognostic survival analysis and used the GEPIA2 database to explore the association between PPP1R14A expression and pathological stages. In addition, cBioPortal and UALCAN databases were employed to analyze the genetic alterations and post-transcriptional phosphorylation of PPP1R14A. Then based on TCGA, we analyzed the relationship between PPP1R14A and immune infiltration, the correlation with tumor mutational burden (TMB), microsatellite instability (MSI) and immune checkpoint molecules (ICMs), and whether it is expected to be a predictive indicator in cancer patients, which was achieved by receiver operating characteristic (ROC) curve. Finally, STRING, GEPIE2 and TIMER2.0 databased were used to explore the potential mechanism of PPP1R14A in cancer and find molecules that have potential close interactions with PPP1R14A.ResultsPPP1R14A is down-expressed in major malignancies and there is a significant correlation between the PPP1R14A expression and the prognosis of patients. Pan-cancer survival analysis indicated that the high expression of PPP1R14A in most cases was associated with poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) across patients with various malignant tumors, containing adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA). The results of ROC analysis subsequently exhibited that the molecule has a high reference significance in diagnosing a variety of cancers. Besides, we detected that the frequency of PPP1R14A genetic changes including genetic mutations and copy number alterations (CNAs) in uterine carcinosarcoma reached 16.07%, and these alterations brought misfortune to the survival and prognosis of cancer patients. In addition, the methylation within the promoter region of PPP1R14A DNA was enhanced in a majority of cancers. Downregulated phosphorylation levels of phosphorylation sites including S26, T38, etc. in most cases took place in several tumors, such as breast cancer, colon cancer, etc. PPP1R14A remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. ConclusionsOur research summarized and analyzed the carcinogenic effect of PPP1R14A in different tumors comprehensively and provided a theoretical basis for promising therapeutic and immunotherapy strategies.

scholarly journals Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy

2020 ◽  
Vol 21 (5) ◽  
pp. 1850 ◽  
Author(s):  
Seung-Woo Baek ◽  
In-Hwan Jang ◽  
Seon-Kyu Kim ◽  
Jong-Kil Nam ◽  
Sun-Hee Leem ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Survival Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Urothelial Cancer ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Prognostic Impact ◽  
T Effector Cells ◽  
Advanced Urothelial Cancer

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8+ T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy.

Analysis of Toxicity Profile and Predictors of Immune Checkpoint Inhibitor-Related Adverse Events

2020 ◽  
Author(s):  
Rilan Bai ◽  
Naifei Chen ◽  
Xiao Chen ◽  
Lingyu Li ◽  
Wei Song ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Toxicity Profile ◽  
Baseline Characteristics ◽  
Pan Cancer

Abstract Background and objectiveIn recent years, a wide variety of immune checkpoint inhibitors (ICIs) is emerging and has shown long-lasting and significant efficacy in the treatment of various malignant tumors. However, about 10% of patients experience serious and even life-threatening immune-related adverse events (irAEs). Fully understanding the characteristics of toxic effects and biomarkers to predict irAEs is, therefore, of great interest. We aimed to retrospectively analyze the toxicity profile and predictors of irAEs, as well as the correlation between irAEs and clinical efficacy in patients with advanced pan-cancer who were treated with multi-type ICIs in real-world.MethodsWe retrospectively analyzed data from 105 patients with advanced pan-cancer who were treated with multi-type ICIs in the First Hospital of Jilin University from Jan 1, 2016 to Aug 1, 2020. We used logistic regression analyses to investigate associations between irAEs and clinical baseline characteristics, blood count parameters, and biochemical indicators during the treatment. Receiver-operating characteristic (ROC) curve was used to determine a cutoff value for parameters and area under the curve (AUC). Kaplan–Meier and cox multivariate regression analysis were performed to estimate the relationship of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS).ResultsWe found that lower relative lymphocyte count (RLC) (cutoff=0.285*10^9/L), higher albumin (ALB) (cutoff=39.05g/L) and higher absolute eosinophil count (AEC) (cutoff=0.175*10^9/L) were significantly associated with the occurrence of any irAEs, of which a higher AEC (cutoff=0.205*10^9/L) was strongly associated with skin-related irAEs (HR=0.163, p=0.004); And a higher lactate dehydrogenase (LDH) level (cutoff=237.5U/L) was an independent predictor of serious irAEs (HR=0.199, p=0.022). In the analysis of immune cell subgroup, lower absolute CD8+CD28- T cell count (HR=0.806; 95%CI: 0.643-1.011; p=0.062), a regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant; And a higher percentage of CD19+ B cells were associated with the occurrence of serious irAEs and irAEs of grade ≥2 (p＜0.05). In addition, our study showed that patients with any grade irAE had a significantly better PFS (8.37 vs.3.77 months, HR=2.02, p=0.0038) and OS (24.77 vs.13.83 months, HR=1.78, p=0.029).ConclusionsThis retrospective study reported the clinical profile data of irAEs of unselected patients in the real world, and explored some parameters that may all be conventional, potentially predictable markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may contribute to fully assess the risk-benefit ratio for patients treated with ICIs.

scholarly journals Results from a Meta-analysis of Combination of PD-1/PD-L1 and CTLA-4 Inhibitors in Malignant Cancer Patients: Does PD-L1 Matter?

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqian Feng ◽  
Huimin Jin ◽  
Kaibo Guo ◽  
Yuying Xiang ◽  
Yiting Zhang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Immunotherapy

Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been widely used for clinical treatment in recent years, which has a better survival benefit. However, not all patients can derive clinical benefit from combination immunotherapy. Therefore, it is necessary to explore the biomarkers of combination immunotherapy.Methods: We retrieved articles from electronic databases including PubMed, EMBASE and Cochrane. The statistical analysis was performed using RevMan software. Progression free survival (PFS), overall survival (OS) and objective response rate (ORR) were the outcome indicators. In the unselect population, we compared combination therapy with other treatments. In addition, we also conducted subgroup analysis on PFS, OS and ORR according to PD-L1 status.Results: Seven studies were included in the analysis for a total of 3,515 cases. In the unselected population, we found that combination therapy has longer PFS, OS, and better ORR than other treatments for cancer patients. The longer PFS was showed in PD-L1 ≥ 5% cases (HR = 0.64, 95% CI: 0.56–0.76; p < 0.001) than PD-L1 ≥ 1% cases (HR = 0.72, 95% CI: 0.66–0.79; p < 0.001), while ORR and OS have not related to the status of PD-L1.Conclusion: This study supported the efficacy of combination therapy with immune checkpoint inhibitors (ICIs), and also showed that PFS in patients with malignant tumors is positively correlated with PD-L1 expression. Due to the limited number of trials included, more high-quality clinical randomized controlled trials should be conducted to confirm the review findings.

scholarly journals Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10612
Author(s):  
Yi-Fang Yang ◽  
Hao-Wen Chuang ◽  
Wei-Ting Kuo ◽  
Bo-Syuan Lin ◽  
Yu-Chan Chang
Keyword(s):  
Urothelial Cancer ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Clinical Applications ◽  
Glycolytic Enzymes ◽  
Metabolic Reprogramming ◽  
Urinary System ◽  
Aberrant Expression ◽  
Genetic Changes ◽  
Upper Tract Urothelial Cancer

Urothelial cancer is a malignant tumor with metastatic ability and high mortality. Malignant tumors of the urinary system include upper tract urothelial cancer and bladder cancer. In addition to typical genetic alterations and epigenetic modifications, metabolism-related events also occur in urothelial cancer. This metabolic reprogramming includes aberrant expression levels of genes, metabolites, and associated networks and pathways. In this review, we summarize the dysfunctions of glycolytic enzymes in urothelial cancer and discuss the relevant phenotype and signal transduction. Moreover, we describe potential prognostic factors and risks to the survival of clinical cancer patients. More importantly, based on several available databases, we explore relationships between glycolytic enzymes and genetic changes or drug responses in urothelial cancer cells. Current advances in glycolysis-based inhibitors and their combinations are also discussed. Combining all of the evidence, we indicate their potential value for further research in basic science and clinical applications.

scholarly journals Prognostic Value and Immune Characteristics of RUNX Family in Human Cancers: A Pan-cancer Analysis

2021 ◽  
Author(s):  
Han Zhao ◽  
Yun Chen ◽  
Peijun Shen ◽  
Lan Gong
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Cancer Types ◽  
Pan Cancer

Abstract Background: Runt‑related transcription factors (RUNX) are involved in numerous fundamental biological processes and play crucial parts in tumorigenesis and metastasis both directly and indirectly. However, the pan-cancer evidence of RUNX gene family is no available. Methods: In this study, we analyzed the potential association between RUNX gene family expression and patient’s prognosis, immune cell infiltration, drug response, and genetic mutation data across different types of tumors using based on The Cancer Genome Atlas, Gene Expression Omnibus, and Oncomine database. Results: The results showed that the expression of the RUNX family varied among different cancer types, revealing its heterogeneity in cancers, and that expression of RUNX2 was lower than that of RUNX1 and RUNX3 across all cancer types. RUNX family gene expression was related to prognosis in several cancers. Furthermore, our study revealed a clear association between RUNX family expression and ESTIMATE score, RNA stemness, and DNA stemness scores. Compared with RUNX1 and RUNX2, RUNX3 showed relatively low levels of genetic alterations. RUNX family genes had clear associations with immune infiltrate subtypes, and their expression was positively related to immune checkpoint genes and drug sensitivity in most cases. Conclusions: These findings will help to elucidate the potential oncogenic roles of RUNX family genes in different types of cancer and it can function as a prognostic marker in various malignant tumors.

scholarly journals Pan-Cancer Analysis Revealed SRSF9 as a New Biomarker for Prognosis and Immunotherapy

2022 ◽  
Vol 2022 ◽  
pp. 1-21
Author(s):  
Jinhui Liu ◽  
Yuanyuan Wang ◽  
Jian Yin ◽  
Yan Yang ◽  
Rui Geng ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Negative Relationship ◽  
Dna Methyltransferases ◽  
Gene Set Enrichment Analysis ◽  
Mmr Genes ◽  
Free Interval ◽  
Cancer Types ◽  
Immune Score ◽  
Pan Cancer

Background. Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. However, whether SRSF9 has a crucial role across pan-cancer is still unknown. Methods. In this study, we used public databases, such as The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx), to analyze SRSF9 expression level among tumor and normal cells. Survival analysis, K-M plotter, and PrognoScan were used to analyze the prognosis value of SRSF9, regarding to overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Moreover, we performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. Results. In general, SRSF9 expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which SRSF9 was associated with short survival and severe progression. In COAD, STAD, and UCEC, SRSF9 expression was positively related to both TMB and MSI. In BRCA, BLCA, ESCA, GBM, HNSC, LUSC, LUAD, OV, PRAD, TGCT, THCA, and UCEC, both immune score and stomal score showed a negative relationship with SRSF9 expression. Immune score showed a positive relationship with SRSF9 expression in LGG. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In LIHC, SRSF9 was highly significant correlated with most immune checkpoint genes. For neoantigens, correlation between SRSF9 and the quantity of neoantigens was significantly positive in some cancer types. SRSF9 was also correlated with MMR genes, m6A genes, and DNA methyltransferases. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. Conclusion. These findings demonstrated that SRSF9 may be a new biomarker for the prognosis and immunotherapy in various cancers. As a result, it will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients.

Study on influencing factors and survival analysis of patients with malignant tumors treated by music therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23144-e23144
Author(s):  
Lei Hong ◽  
Junyan Wang ◽  
Fan Zhang ◽  
Minting Ma ◽  
Da Jiang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Music Therapy ◽  
Cancer Patients ◽  
Influencing Factors ◽  
Significant Influence ◽  
Malignant Tumors ◽  
Therapy Group ◽  
Intervention Group ◽  
Education Level ◽  
Control Group

e23144 Background: Music therapy is not easy to carry out. After carrying out music therapy propaganda, many patients still question the efficacy of it, and won’t be included in music therapy group. This study retrospectively analyzed the related factors and survival analysis of patients enrolled in music therapy, and provided reference for appropriate music therapy propaganda methods. Methods: From March 2014 to January 2016, 258 patients with malignant tumors diagnosed in Fourth Hospital of Hebei Medical University were collected. Music therapy was divided into control group and intervention group according to whether they were willing to be included in the group or not. Questionnaire survey was used to investigate the effect of factors on music therapy in the two groups. Follow-up was conducted by telephone to analyze the effect of music therapy on PFS. Single factor analysis was used to analyze the relationship between factors and music therapy. The differences of PFS between control group and intervention group was analyzed by Log-Rank test (P < 0.05). Results: A total of 258 patients were enrolled in the questionnaire survey, and 240 patients completed the questionnaire effectively. Age, education level, music hobby, and knowledge of illness had significant influence on whether the patients were enrolled in music therapy group (P < 0.05). Gender, occupation, type of disease, stage of disease and DT score had no significant effect on whether patients were enrolled in music therapy group (P > 0.05). Age and music preference were independent influencing factors of music therapy (P = 0.025, P = 0.000). The median PFS of lung cancer patients was 8 months and 8 months, respectively (P = 0.760). The median PFS of breast cancer patients was 9 months and 8 months, respectively (P = 0.726). The median PFS of digestive tract cancer patients was 8 months and 10 months, respectively (P = 0.684). The median PFS of gynecologic tumor patients was 8 months and 8 months, respectively (P = 0.310). Conclusions: Age, education level, music hobby and condition information have significant influence on whether patients are included in music therapy group or not. Age and music hobby are independent influencing factors of music therapy. PFS of patients with malignant tumors who are willing to be included in music therapy group tends to prolong, but there is no statistical significance.

A pan-cancer analysis of ARID1A as a potential biomarker for immune checkpoint therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3540-3540
Author(s):  
Dongyong Yang ◽  
Yuan Xu ◽  
Linlin Huang ◽  
Zhifeng Guo ◽  
Jimin Fan ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gene Mutation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Study Cohort ◽  
Tumor Type ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Ngs Data ◽  
Pan Cancer

3540 Background: AT-rich interactive domain 1A (ARID1A), encoding a subunit of the BAF (SWI/SNF) chromatin remodeling complex, is correlated with the origination and progress of tumor. Previous research on ARID1A gene revealed that ARID1A deficiency was associated with mismatch repair (MMR) and higher tumor mutation burden (TMB) level in cancer, which might cooperate with immune checkpoint blockade therapy. Methods: Next generation sequencing (NGS) data of 10336 pan-cancer patients were obtained from the MSK-IMPACT Clinical Sequencing cohort (MSKCC). NGS data of 15849 pan-cancer patients from Chinese clinical dataset were analyzed to explore the association between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. 853 advanced NSCLC patients from two independent cohorts (OAK study cohort and POPLAR study cohort) were used to analyze the correlation between ARID1A alteration and the efficacy of immune checkpoint blockade immunotherapies (ICIs). Results: In total, 8.62% (891/10336) of pan-cancer patients in MSKCC harbored ARID1A mutation and 8.47% (3188/37628) in Chinese cohort. In MSKCC cohort, the highest ARID1A mutation frequency tumor type was endometrial cancer (31.64%, 69/218), bladder cancer (26.95%, 114/423) and hepatobiliary cancer (17.18%, 61/355) come in second and third, respectively. While in Chinese cohort, the top three ARID1A mutation frequency tumor types were endometrial cancer (39.29%, 88/224), gastric carcinoma (17.80%, 318/1787) and urothelial carcinoma (17.18%, 83/483), respectively. ARID1A gene mutation was also associated with higher TMB in the Chinese pan-cancer cohort (P < 0.0001). The highest medium TMB level of ARID1A mutation tumor type was Urothelial carcinoma with 18.63 Muts/Mb (n = 65). In addition, the TMB level and prognositic analysis were performed on patients in two independent NSCLC cohorts with ICIs, TMB level of ARID1A mutant group was higher than wild-type group with significant difference (P < 0.0001). The overall survival (OS) of ARID1A mutation group were significantly shorter than wild-type group (OS, median, 6.80 vs 10.28 months; HR, 1.47; P = 0.0474), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 1.46 vs 2.99 months; HR, 1.27; P = 0.1584). Conclusions: The results indicated that ARID1A gene mutation was associated with a higher TMB level in Chinese pan-cancer patients, and patients harboring these genes mutations might easily benefit from ICIs.

scholarly journals Investigate the relevance of major signaling pathways in cancer survival using a biologically meaningful deep learning model

2020 ◽  
Author(s):  
Jiarui Feng ◽  
Heming Zhang ◽  
Fuhai Li
Keyword(s):  
Survival Analysis ◽  
Deep Learning ◽  
Survival Time ◽  
Signaling Pathways ◽  
Cancer Patients ◽  
Cancer Survival ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Survival Prediction ◽  
Cancer Signaling

AbstractSurvival analysis and prediction are important in cancer studies. In addition to the Cox proportional hazards model, recently deep learning models have been proposed to integrate the multi-omics data for survival prediction. Cancer signaling pathways are important and interpretable concepts that define the signaling cascades regulating cancer development and drug resistance. Thus, it is interesting and important to investigate the relevance to patients’ survival of individual signaling pathways. In this exploratory study, we propose to investigate the relevance and difference of a small set of core cancer signaling pathways in the survival analysis of cancer patients. Specifically, we built a biologically meaningful and simplified deep neural network, DeepSigSurvNet, for survival prediction. In the model, the gene expression and copy number data of 1648 genes from 46 major signaling pathways are used. We applied the model on 4 types of cancer and investigated the relevance and difference of the 46 signaling pathways among the 4 types of cancer. Interestingly, the interpretable analysis identified the distinct patterns of these signaling pathways, which are helpful to understand the relevance of the signaling pathways in terms of their association with cancer survival time. These highly relevant signaling pathways can be novel targets, combined with other essential signaling pathways inhibitors, for drug and drug combination prediction to improve cancer patients’ survival time.

scholarly journals Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1271
Author(s):  
Alexander Malogolovkin ◽  
Nizami Gasanov ◽  
Alexander Egorov ◽  
Marianna Weener ◽  
Roman Ivanov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Immune Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Conventional Radiotherapy ◽  
Indispensable Tool

Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials evaluating oncolytic viruses with or without genetic alterations in combination with immune checkpoint blockade, cytokines, antigens and other oncolytic viruses as well. This review is focused on the efficacy and safety of virotherapy and the most promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations, which are discussed in comprehensive literature reviews. We briefly revise the research landscape of oncolytic viruses and discuss future perspectives in virus immunotherapy, in order to provide an insight for novel strategies of cancer treatment.

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