Immune checkpoint proteins (PD-L1 and CTLA-4) in endometrial carcinoma: prognostic role and correlation with CD4<sup>+</sup>/CD8<sup>+</sup> tumor infiltrating lymphocytes (TILs) ratio

Khalifa, Rana; Elsese, Nawal; El-Desouky, Karima; Shaair, Hassan; Helal, Duaa S

doi:10.1080/15321819.2021.1981377

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…Nevertheless, the impact of the balance between CD4 + T and CD8 + T in peripheral blood of cancer patients on ICI therapies is still unclear. In endometrial carcinoma, the CD4 + /CD8 + TILs ratio has been reported to be significantly associated with expression of immune checkpoint proteins such as cytotoxic T-lymphocyte associated protein 4(CTLA-4) and PD-L1 [35]. The pre-treatment CD4 + /CD8 + TILs ratio by immunohistochemistry on gastric cancer tissues revealed a remarkable correlation with lymphovascular invasion, TNM stage and response to neoadjuvant chemotherapy, and lower CD4 + /CD8 + TILs ratio predicted significantly better survival outcomes [36].…”

Section: Discussionmentioning

confidence: 99%

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Liu,

et al. 2023

Cancer Cell Int

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Background Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy. Methods A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People’s Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan–Meier methods and Cox proportional hazards regression models. Results The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy. Conclusion The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.

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Section: Discussionmentioning

confidence: 99%

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Liu,

et al. 2023

Cancer Cell Int

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“…There is compelling evidence to support the use of CTLA4 inhibitors in UCEC. However, clinical data on the effectiveness of molecules such as Ipilimumab, the anti-CTLA4 monoclonal antibodies, has not yet been published ( Khalifa et al, 2022 ). Despite the fact that the use of CTLA4 inhibitors has a solid justification in UCEC, clinical data on the effectiveness of molecules such as Ipilimumab and Tremelimumab, two anti-CTLA4 monoclonal antibodies, have yet to be disclosed ( Nishio et al, 2021 ; Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer

He²,

Luo

et al. 2022

Front. Cell Dev. Biol.

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A better knowledge of the molecular process behind uterine corpus endometrial carcinoma (UCEC) is important for prognosis prediction and the development of innovative targeted gene therapies. The purpose of this research is to discover critical genes associated with UCEC. We analyzed the gene expression profiles of TCGA-UCEC and GSE17025, respectively, using Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. From four sets of findings, a total of 95 overlapping genes were retrieved. On the 95 overlapping genes, KEGG pathway and GO enrichment analysis were conducted. Then, we mapped the PPI network of 95 overlapping genes using the STRING database. Twenty hub genes were evaluated using the Cytohubba plugin, including NR3C1, ATF3, KLF15, THRA, NR4A1, FOSB, PER3, HLF, NTRK3, EGR3, MAPK13, ARNTL2, PKM2, SCD, EIF5A, ADHFE1, RERGL, TUB, and ENC1. The expression levels of NR3C1, PKM2, and ENC1 were shown to be adversely linked with the survival time of UCEC patients using univariate Cox regression analysis and Kaplan-Meier survival calculation. ENC1 were also overexpressed in UCEC tumor tissues or cell lines, as shown by quantitative real-time PCR and Western blotting. Then we looked into it further and discovered that ENC1 expression was linked to tumor microenvironment and predicted various immunological checkpoints. In conclusion, our data indicate that ENC1 may be required for the development of UCEC and may serve as a future biomarker for diagnosis and therapy.

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“…CTLA-4 is expressed exclusively in T cells, where it dampens the activation of T cells by outcompeting CD28 in binding to CD80 and CD86, as well as actively delivering inhibitory signals to the T cells [ 294 ]. The expression of CTLA-4 seems to be higher than that of PD-L1 and is associated with a low CD4 + /CD8 + ratio and high tumor grade in EC [ 295 ].…”

Section: Immunotherapeutic Strategies For Gynecological Cancersmentioning

confidence: 99%

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

Zhang

Sheng

Sun

et al. 2023

Cancer Metastasis Rev

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Advanced and recurrent gynecological cancers lack effective treatment and have poor prognosis. Besides, there is urgent need for conservative treatment for fertility protection of young patients. Therefore, continued efforts are needed to further define underlying therapeutic targets and explore novel targeted strategies. Considerable advancements have been made with new insights into molecular mechanisms on cancer progression and breakthroughs in novel treatment strategies. Herein, we review the research that holds unique novelty and potential translational power to alter the current landscape of gynecological cancers and improve effective treatments. We outline the advent of promising therapies with their targeted biomolecules, including hormone receptor-targeted agents, inhibitors targeting epigenetic regulators, antiangiogenic agents, inhibitors of abnormal signaling pathways, poly (ADP-ribose) polymerase (PARP) inhibitors, agents targeting immune-suppressive regulators, and repurposed existing drugs. We particularly highlight clinical evidence and trace the ongoing clinical trials to investigate the translational value. Taken together, we conduct a thorough review on emerging agents for gynecological cancer treatment and further discuss their potential challenges and future opportunities.

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Immune checkpoint proteins (PD-L1 and CTLA-4) in endometrial carcinoma: prognostic role and correlation with CD4⁺/CD8⁺ tumor infiltrating lymphocytes (TILs) ratio

Cited by 6 publications

References 43 publications

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

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Immune checkpoint proteins (PD-L1 and CTLA-4) in endometrial carcinoma: prognostic role and correlation with CD4+/CD8+ tumor infiltrating lymphocytes (TILs) ratio

Cited by 6 publications

References 43 publications

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

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Product

Resources

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Immune checkpoint proteins (PD-L1 and CTLA-4) in endometrial carcinoma: prognostic role and correlation with CD4⁺/CD8⁺ tumor infiltrating lymphocytes (TILs) ratio