Prognostic value of tumour-associated regulatory T-cells as a biomarker in non-small cell lung cancer: a systematic review and meta-analysis

Background: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg).

Methods: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR).

Results: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) < .001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p = .01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed) .034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed) .009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC.

Conclusion: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC.

Systematic review registration: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website.