Immune Checkpoint Inhibitor Therapy in Oncology

Tan, Sean; Day, Daphne; Nicholls, Stephen J.; Segelov, Eva

doi:10.1016/j.jaccao.2022.09.004

Cited by 47 publications

(29 citation statements)

References 161 publications

(151 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some concern exists on potential CV toxicity with ICI therapy in detail [ 43 ]. As ICI is more frequently prescribed, the ongoing reporting and prevalence of diagnosis-related CV toxicity changes, so useful data and recommendations evolve rapidly [ 44 , 45 ]. ICIs are relevant in a variety of cancer diseases, such as melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma.…”

Section: Resultsmentioning

confidence: 99%

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs

Palmieri

Vietri

Montalto

et al. 2023

Cancers

View full text Add to dashboard Cite

Background: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. Methods: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. Results: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. Conclusions: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor.

show abstract

Section: Resultsmentioning

confidence: 99%

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs

Palmieri

Vietri

Montalto

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…In the immunotherapy of MM patients, except pembrolizumab, several other ICIs have been administered, including nivolumab (anti-PD-1 mAb) and atezolizumab (anti-PD-L1 mAb) alone, or in combination with conventional chemotherapeutics and/or IMIDs, which are showing a disappointing clinical response in the majority of cases [ 23 , 55 ]. Available data showed that the low efficacy of conventional checkpoint inhibitors may be caused by the existence of compensatory inhibitory mechanisms related to the up-regulation of the other checkpoints, such as VISTA or TIM-3 [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Inappropriate Expression of PD-1 and CTLA-4 Checkpoints in Myeloma Patients Is More Pronounced at Diagnosis: Implications for Time to Progression and Response to Therapeutic Checkpoint Inhibitors

Nałęcz

Ciszak

Usnarska−Zubkiewicz

et al. 2023

IJMS

View full text Add to dashboard Cite

Multiple myeloma (MM) is a hematologic malignancy characterized by severely profound immune dysfunction. Therefore, the efficacy of drugs targeting the immune environments, such as immune checkpoint inhibitors (ICIs), is of high clinical importance. However, several clinical trials evaluating ICIs in MM in different therapeutic combinations revealed underwhelming results showing a lack of clinical efficacy and excessive side effects. The underlying mechanisms of resistance to ICIs observed in the majority of MM patients are still under investigation. Recently, we demonstrated that inappropriate expression of PD-1 and CTLA-4 on CD4 T cells in active MM is associated with adverse clinical outcomes and treatment status. The aim of the current study was to determine the usefulness of immune checkpoint expression assessment as a predictive biomarker of the response to therapeutic inhibitors. For this purpose, along with checkpoint expression estimated by flow cytometry, we evaluated the time to progression (TTP) of MM patients at different clinical stages (disease diagnosis and relapse) depending on the checkpoint expression level; the cut-off point (dividing patients into low and high expressors) was selected based on the median value. Herein, we confirmed the defective levels of regulatory PD-1, CTLA-4 receptors, and the CD69 marker activation in newly diagnosed (ND) patients, whereas relapsed/refractory patients (RR) exhibited their recovered values and reactivity. Additionally, substantially higher populations of senescent CD4+CD28− T cells were found in MM, primarily in NDMM subjects. These observations suggest the existence of two dysfunctional states in MM CD4 T cells with the predominance of immunosenescence at disease diagnosis and exhaustion at relapse, thus implying different responsiveness to the external receptor blockade depending on the disease stage. Furthermore, we found that lower CTLA-4 levels in NDMM patients or higher PD-1 expression in RRMM patients may predict early relapse. In conclusion, our study clearly showed that the checkpoint level in CD4 T cells may significantly affect the time to MM progression concerning the treatment status. Therefore, when considering novel therapies and potent combinations, it should be taken into account that blocking PD-1 rather than CTLA-4 might be a beneficial form of immunotherapy for only a proportion of RRMM patients.

show abstract

“…3.8. INF2 exhibited signi cant associations with TMB, MSI, NEO, predicted the therapeutic e cacy of immunotherapy, and re ected mutation pro les TMB, MSI, and NEO are emerging biomarkers associated with tumor response to immunotherapy [40]. Therefore, we investigated the relationship between the INF2 and TMB, MSI, as well as NEO.…”

Section: Enhanced Correlation Between the Expression Of Inf2 And Cruc...mentioning

confidence: 99%

A transcriptomic pan-cancer signature for potential implications in prognosis and treatment based on disulfidptosis-related gene

Xu,

Xie,

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Disulfidptosis is a new type of regulated cell death that involves cytoskeletal collapse, induced by excessive disulfide bond formation. However, understanding of the biological characteristics and clinical significance of disulfidptosis in pan-cancers remains limited. Methods We obtained transcriptome data from TCGA via UCSC Xena. Based on the expression of disulfidptosis-related genes (DRG), we constructed a consensus DRG-related signature (DRGS) using the LASSO Cox regression model. A nomogram incorporating the DRG score was developed as a quantitative tool for predicting prognosis. We utilized the z-score algorithm to integrate gene expression characteristics and activity of specific pathways. Comprehensive analyses were performed to investigate tumor microenvironment and mutation profiles. We evaluated the responses of subgroups to immunotherapy and conducted drug screening. Finally, we utilized immunofluorescence (IF) to evaluate the expression of hub genes in patients with ovarian cancer (OV). Results The DRGS was considered a prognostic factor for various types of cancer, with higher scores indicating more unfavorable outcomes. DRGS can also serve as a predictive indicator for various malignant biological processes. The independent prognostic significance for survival was confirmed using multivariate analysis. The group characterized by high expression levels of inverted formin 2 (INF2) demonstrated an attenuated response to palbociclib treatment and an immunosuppressive phenotype. In OV, INF2 was associated with poor clinical outcomes. Conclusion Our study demonstrated a prognostic DRGS, which holds great promise as a robust tool for uncovering clinical characteristics, predicting survival outcomes, and reflecting the response to targeted therapy across various cancer types.

show abstract

Immune Checkpoint Inhibitor Therapy in Oncology

Cited by 47 publications

References 161 publications

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs

Inappropriate Expression of PD-1 and CTLA-4 Checkpoints in Myeloma Patients Is More Pronounced at Diagnosis: Implications for Time to Progression and Response to Therapeutic Checkpoint Inhibitors

A transcriptomic pan-cancer signature for potential implications in prognosis and treatment based on disulfidptosis-related gene

Contact Info

Product

Resources

About