Immunotherapy Advances for Epithelial Ovarian Cancer

Hartnett, Erin; Knight, Julia; Radolec, Mackenzy; Buckanovich, Ronald J.; Edwards, Robert P.; Vlad, Anda

doi:10.3390/cancers12123733

Cited by 30 publications

(26 citation statements)

References 151 publications

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“…Since the FDA approved ipilimumab for advanced melanoma in 2011, the last ten years have been characterized by the widespread use of ICIs, thus revolutionizing the therapeutic algorithm of many solid tumors [10,37]. ICIs are monoclonal antibodies that unlock the anti-tumoral response of the host immune system through the inhibition of negative signals for effector T-cells.…”

Section: Resultsmentioning

confidence: 99%

“…However, limited benefits have emerged in the OC, even leading to the premature termination for the futility of some studies. Different components of the OC tumor microenvironment (TME) contribute to this failure, such as myeloid-derived suppressor cells (MDSCs), tumorassociated macrophages (TAMs), T-cells, cytokines, and soluble factors [37][38][39][40]. MDSCs exert immunosuppressive functions, such as the inhibition of T-effector and natural killer (NK)-cells, and are induced under pro-inflammatory cytokines, IFNγ, tumor necrosis factor-alpha (TNFα), interleukin (IL)-6 [41].…”

Section: Discussionmentioning

confidence: 99%

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Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

Maiorano

Lorusso

et al. 2021

Preprint

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Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In the advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in the OC. Methods: We searched the PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were selected, of which 16 were phase I or II and 4 phase III trials. ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, atezolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab) were employed. No significant survival improvement was achieved; conversely, early terminations due to futility or toxicity were recorded. Combinations with chemotherapy, anti-VEGF, and, overall, PARP-inhibitors seem feasible and enhance the response rate and survival, notwithstanding a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of the OC might lead to an improved treatments selection and design of tailored trials.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

Maiorano

Lorusso

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…However, limited benefits have emerged in OC, even leading to premature termination due to the futility of some studies. Different components of the OC tumor microenvironment (TME) contribute to this failure, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), T-cells, cytokines, and soluble factors [37][38][39][40]. MDSCs exert immunosuppressive functions, such as the inhibition of T-effector and natural killer (NK)-cells, and are induced under proinflammatory cytokines, IFNγ, tumor necrosis factor-alpha (TNFα), interleukin (IL)-6 [41].…”

Section: Discussionmentioning

confidence: 99%

“…The incidence is around 11 cases/100,000 inhabitants/year, and it is higher among white women [1,2]. The frequency of OC rises with Since the FDA approved ipilimumab for advanced melanoma in 2011, the last ten years were characterized by the widespread use of ICIs, revolutionizing the therapeutic algorithm for many solid tumors [10,37]. ICIs are monoclonal antibodies that promote the anti-tumoral response of the host immune system through the inhibition of negative signals for effector T-cells.…”

Section: Introductionmentioning

confidence: 99%

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives

Maiorano

Lorusso

et al. 2021

Cancers

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Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC. Methods: We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials.

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“…Notably, AML is composed not only of leukemic cells but also of nonleukemic cells, in which the immune microenvironment may play an important role in promoting the development and recurrence of AML [18]. In recent years, several promising preclinical and clinical immunotherapies, including immune checkpoint inhibitors and active or passive immunotherapies, have shown promising results in a variety of cancers, but the effect is not obvious for AML, suggesting that AML has a unique mechanism to evade treatment [19][20][21][22][23]. To better understand the role of immunity in AML, we summarized the number of immune cells in AML from the perspective of the diversity and nature of infiltrating immune cells in AML.…”

Section: Introductionmentioning

confidence: 99%

Identification of Prognosis-Related Genes of Acute Myeloid Leukemia

Zhou¹,

Chen²

2021

COR

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Background: Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous hematological malignancy and relapse is the main reason for the poor therapeutic effect and low survival rate. Bioinformatic technology could screen out relative genes that promote the recurrence of AML, providing a theoretical basis for further improving the precision stratification treatment of AML. Methods: In this study, gene expression profiles of Dataset Acute Myeloid Leukemia (OHSU, Nature 2018) and GSE134589 were downloaded from cBioPortal and GEO, respectively. R software and limma packages were used to identify the DEGs and then run GO enrichment, KEGG pathway, and PPI network. CIBERSORTx was used to enumerate tumor-infiltrating immune cells. Prognosis-related genes were selected by univariate and multivariate Cox proportional hazards regression analyses and the expression of them were verified by GEPIA. Kaplan-Meier curve analysis could compare the survival time. ROC curve analysis was performed to predict the value of the selected genes. Results: Functional analysis showed that the up-regulated DEGs were strikingly enriched in Cytokine-cytokine receptor interaction and positive regulation of cytokine production, and the down-regulated DEGs in the regulation of cell-cell adhesion, TNF signaling pathway. CIBERSORTx analysis revealed that the immune response of AML acted as an intricate network and proceeded in a tightly regulated way. Cox analysis showed that ALDH1L2, KLK1, and LRRN2 were correlated with AML prognosis. Conclusion: ALDH1L2, KLK1, and LRRN2 are prognosis-related genes in AML, which may, together with some immune pathways, induce poor prognosis and can be used as potential biomarkers in AML treatment.

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Immunotherapy Advances for Epithelial Ovarian Cancer

Cited by 30 publications

References 151 publications

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives

Identification of Prognosis-Related Genes of Acute Myeloid Leukemia

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