The Predictive and Prognostic Nature of Programmed Death-Ligand 1 in Malignant Pleural Mesothelioma: A Systematic Literature Review

Mansfield, Aaron S.; Brown, Rebecca; Sammon, Cormac; Daumont, M.; McKenna, Mike; Sanzari, Jenine K.; Forde, Patrick M.

doi:10.1016/j.jtocrr.2022.100315

Cited by 10 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2020, a combination of anti-PD-1 mAb nivolumab plus anti-CTLA-4 mAb ipilimumab was approved by the U.S. Food and Drug Administration (FDA) as a first-line therapy for unresectable MPM (7,15,16). Whereas initial promising results of mAb-based therapy have changed the landscape of MPM treatment, the efficacy is limited to a certain subset of patients, indicating an urgent need to establish biomarkers for patient selection (17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma

et al. 2023

View full text Add to dashboard Cite

IntroductionMalignant pleural mesothelioma (MPM) is a rare and highly aggressive thoracic tumor with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors exhibit a promising effect in some patients with unresectable MPM in clinical trials, the majority of MPM patients show only modest response rates to the currently available treatments. It is thus imperative to develop novel and innovative therapeutic modalities for MPM, including immune effector cell-based therapies.Methodsγδ T cells were expanded using tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2, and the therapeutic potential of γδ T cells was examined through analyzing cell surface markers and cellular cytotoxicity against MPM in vitro using a europium chelate-based time-resolved fluorescence assay system and a luciferase-based luminescence assay system.Results and discussionWe successfully expanded γδ T cells from peripheral blood mononuclear cells of healthy donors and MPM patients. γδ T cells expressed natural killer receptors such as NKG2D and DNAM-1 and exhibited a moderate level of cytotoxicity to MPM cells in the absence of antigens. The inclusion of PTA, (E)-4-hydroxy-3- methylbut-2-enyl diphosphate (HMBPP) or zoledronic acid (ZOL) induced a TCR-dependent cytotoxicity in γδ T cells and secreted interferon-γ (IFN-γ). In addition, γδ T cells expressing CD16 exhibited a significant level of cytotoxicity against MPM cells in the presence of an anti-epidermal growth factor receptor (EGFR) mAb, at lower concentrations than in clinical settings, whereas a detectable level of IFN-γ was not produced. Taken together, γδ T cells showed cytotoxic activity against MPM in three distinct mechanisms through NK receptors, TCRs and CD16. Since major histocompatibility complex (MHC) molecules are not involved in the recognition, both autologous and allogeneic γδ T cells could be used for the development of γδ T cell-based adoptive immunotherapy for MPM.

show abstract

Section: Discussionmentioning

confidence: 99%

Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Again, given the emergence of program cell death protein-1 (PD-1) pathway blockade as an effective therapeutic option in MPM, there is an increasing interest in which expression of program death ligand 1 (PD-L1) might be prognostic of clinical outcomes. To date, current evidence is still insufficient to draw any definitive conclusion on this topic [ 43 ], but future investigations are required to support the role of PD-L1 in MPM, correlating it to body composition parameters and performance status of the patients.…”

Section: Discussionmentioning

confidence: 99%

Sarcopenia as a Predictor of Short- and Long-Term Outcomes in Patients Surgically Treated for Malignant Pleural Mesothelioma

Faccioli

Terzi

Giraudo

et al. 2022

Cancers

View full text Add to dashboard Cite

Surgery for malignant pleural mesothelioma (MPM) should be reserved only for patients who have a good performance status. Sarcopenia, a well-known predictor of poor outcomes after surgery, is still underinvestigated in MPM. The aim of this study is to evaluate the role of sarcopenia as a predictor of short-and long-term outcomes in patients surgically treated for MPM. In our analysis, we included patients treated with a cytoreductive intent in a multimodality setting, with both pre- and post-operative CT scans without contrast available. We excluded those in whom a complete macroscopic resection was not achieved. Overall, 86 patients were enrolled. Sarcopenia was assessed by measuring the mean muscular density of the bilateral paravertebral muscles (T12 level) on pre-and post-operative CTs; a threshold value of 30 Hounsfield Units (HU) was identified. Sarcopenia was found pre-operatively in 57 (66%) patients and post-operatively in 61 (74%). Post-operative sarcopenic patients had a lower 3-year overall survival (OS) than those who were non-sarcopenic (34.9% vs. 57.6% p = 0.03). Pre-operative sarcopenia was significantly associated with a higher frequency of post-operative complications (65% vs. 41%, p = 0.04). The evaluation of sarcopenia, through a non-invasive method, would help to better select patients submitted to surgery for MPM in a multimodality setting.

show abstract

“…However, the role of PD-L1 tumor expression is still debated. A recent meta-analysis on this topic performed on 29 trials concluded that PD-L1 status was not an established prognostic nor predictive biomarker [ 47 ]. In many trials employing chemotherapy agents, patients with PD-L1 >1% had a higher risk of death compared to their PD-L1-negative counterparts, with a proportional association to the degree of expression [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Gemelli

Cortinovis

Baggi

et al. 2022

Cancers

View full text Add to dashboard Cite

Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13–27%) and 56% (95% CI 45–67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted.

show abstract

The Predictive and Prognostic Nature of Programmed Death-Ligand 1 in Malignant Pleural Mesothelioma: A Systematic Literature Review

Cited by 10 publications

References 40 publications

Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma

Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma

Sarcopenia as a Predictor of Short- and Long-Term Outcomes in Patients Surgically Treated for Malignant Pleural Mesothelioma

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About