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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/19/10389
Description
Summary: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.
ISSN:1661-6596
1422-0067