A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers
Preclinical studies have indicated that T-cell immunoglobulin and ITIM domain (TIGIT) can substantially attenuate anti-tumoral immune responses. Although multiple clinical studies have evaluated the significance of TIGIT in patients with solid cancers, their results remain inconclusive. Thus, we con...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10389 |
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| author | Negar Hosseinkhani Mahdi Abdoli Shadbad Mohammad Asghari Jafarabadi Noora Karim Ahangar Zahra Asadzadeh Seyede Momeneh Mohammadi Parisa Lotfinejad Nazila Alizadeh Oronzo Brunetti Rossella Fasano Nicola Silvestris Behzad Baradaran |
| author_facet | Negar Hosseinkhani Mahdi Abdoli Shadbad Mohammad Asghari Jafarabadi Noora Karim Ahangar Zahra Asadzadeh Seyede Momeneh Mohammadi Parisa Lotfinejad Nazila Alizadeh Oronzo Brunetti Rossella Fasano Nicola Silvestris Behzad Baradaran |
| author_sort | Negar Hosseinkhani |
| collection | DOAJ |
| description | Preclinical studies have indicated that T-cell immunoglobulin and ITIM domain (TIGIT) can substantially attenuate anti-tumoral immune responses. Although multiple clinical studies have evaluated the significance of TIGIT in patients with solid cancers, their results remain inconclusive. Thus, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to determine its significance in patients with solid cancers. We systematically searched the Web of Science, Embase, PubMed, and Scopus databases to obtain peer-reviewed studies published before September 20, 2020. Our results have shown that increased TIGIT expression has been significantly associated with inferior overall survival (OS) (HR = 1.42, 95% CI: 1.11–1.82, and <i>p</i>-value = 0.01). Besides, the level of tumor-infiltrating TIGIT<sup>+</sup>CD8<sup>+</sup> T-cells have been remarkably associated inferior OS and relapse-free survival (RFS) of affected patients (HR = 2.17, 95% CI: 1.43–3.29, and <i>p</i>-value < 0.001, and HR = 1.89, 95% CI: 1.36–2.63, and <i>p</i>-value < 0.001, respectively). Also, there is a strong positive association between TIGIT expression with programmed cell death-1 (PD-1) expression in these patients (OR = 1.71, 95% CI: 1.10–2.68, and <i>p</i>-value = 0.02). In summary, increased TIGIT expression and increased infiltration of TIGIT<sup>+</sup>CD8<sup>+</sup> T-cells can substantially worsen the prognosis of patients with solid cancers. Besides, concerning the observed strong association between TIGIT and PD-1, ongoing clinical trials, and promising preclinical results, PD-1/TIGIT dual blockade can potentially help overcome the immune-resistance state seen following monotherapy with a single immune checkpoint inhibitor in patients with solid cancers. |
| first_indexed | 2024-03-10T06:59:40Z |
| format | Article |
| id | doaj.art-326807c3622c45bc846f7f8ecc4033f0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:40Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-326807c3622c45bc846f7f8ecc4033f02023-11-22T16:08:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191038910.3390/ijms221910389A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid CancersNegar Hosseinkhani0Mahdi Abdoli Shadbad1Mohammad Asghari Jafarabadi2Noora Karim Ahangar3Zahra Asadzadeh4Seyede Momeneh Mohammadi5Parisa Lotfinejad6Nazila Alizadeh7Oronzo Brunetti8Rossella Fasano9Nicola Silvestris10Behzad Baradaran11Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, IranResearch Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, IranDepartment of Statistics and Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan 4513956184, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, IranDepartment of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan 4513956184, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, IranMedical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyMedical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyMedical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyResearch Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, IranPreclinical studies have indicated that T-cell immunoglobulin and ITIM domain (TIGIT) can substantially attenuate anti-tumoral immune responses. Although multiple clinical studies have evaluated the significance of TIGIT in patients with solid cancers, their results remain inconclusive. Thus, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to determine its significance in patients with solid cancers. We systematically searched the Web of Science, Embase, PubMed, and Scopus databases to obtain peer-reviewed studies published before September 20, 2020. Our results have shown that increased TIGIT expression has been significantly associated with inferior overall survival (OS) (HR = 1.42, 95% CI: 1.11–1.82, and <i>p</i>-value = 0.01). Besides, the level of tumor-infiltrating TIGIT<sup>+</sup>CD8<sup>+</sup> T-cells have been remarkably associated inferior OS and relapse-free survival (RFS) of affected patients (HR = 2.17, 95% CI: 1.43–3.29, and <i>p</i>-value < 0.001, and HR = 1.89, 95% CI: 1.36–2.63, and <i>p</i>-value < 0.001, respectively). Also, there is a strong positive association between TIGIT expression with programmed cell death-1 (PD-1) expression in these patients (OR = 1.71, 95% CI: 1.10–2.68, and <i>p</i>-value = 0.02). In summary, increased TIGIT expression and increased infiltration of TIGIT<sup>+</sup>CD8<sup>+</sup> T-cells can substantially worsen the prognosis of patients with solid cancers. Besides, concerning the observed strong association between TIGIT and PD-1, ongoing clinical trials, and promising preclinical results, PD-1/TIGIT dual blockade can potentially help overcome the immune-resistance state seen following monotherapy with a single immune checkpoint inhibitor in patients with solid cancers.https://www.mdpi.com/1422-0067/22/19/10389TIGITPD-1dual blockadeimmune-resistanceimmune checkpointsolid cancers |
| spellingShingle | Negar Hosseinkhani Mahdi Abdoli Shadbad Mohammad Asghari Jafarabadi Noora Karim Ahangar Zahra Asadzadeh Seyede Momeneh Mohammadi Parisa Lotfinejad Nazila Alizadeh Oronzo Brunetti Rossella Fasano Nicola Silvestris Behzad Baradaran A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers International Journal of Molecular Sciences TIGIT PD-1 dual blockade immune-resistance immune checkpoint solid cancers |
| title | A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers |
| title_full | A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers |
| title_fullStr | A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers |
| title_full_unstemmed | A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers |
| title_short | A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers |
| title_sort | systematic review and meta analysis on the significance of tigit in solid cancers dual tigit pd 1 blockade to overcome immune resistance in solid cancers |
| topic | TIGIT PD-1 dual blockade immune-resistance immune checkpoint solid cancers |
| url | https://www.mdpi.com/1422-0067/22/19/10389 |
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