The predictive value of intratumoral tertiary lymphoid structures on the response to immunotherapy in cancer patients: a systematic review and meta-analysis.

BACKGROUND

An increasing number of studies have demonstrated tertiary lymphoid structures (TLS) was associated with prognosis and therapeutic response of immunotherapy in cancer patients. This meta-analysis aimed to investigate the predictive value of intratumoral TLS on the response to immunotherapy in cancer patients and provide evidence regarding the potential of TLS as a novel predictive biomarker for immunotherapy efficacy.

METHODS

A systematic literature search was performed based on three databases (PubMed, EMBASE, and the Cochrane Library) to identify eligible studies up to January 5th, 2024. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated to evaluate the predictive value of TLS expression levels on the response to immunotherapy in cancer patients. Subgroup analysis, publication bias and sensitivity analysis were subsequently performed.

RESULTS

A total of 15 studies with 1,307 cancer patients were included in this meta-analysis. Increased levels of intratumoral TLS were associated with higher positive response rates in cancer patients treated with immunotherapy (OR = 4.21, 95% CI: 2.45-7.21, P < 0.001). In addition, higher intratumoral TLS levels were associated with better overall survival (HR = 0.67, 95% CI: 0.54-0.83, P < 0.001), progression-free survival (HR = 0.63, 95% CI: 0.52-0.75, P < 0.001), and disease-free survival (HR = 0.08, 95% CI: 0.03-0.23, P < 0.001) in cancer patients receiving immunotherapy. The robustness and reliability of the results were confirmed through publication bias and sensitivity analysis.

CONCLUSIONS

High expression of TLS in tumor tissues was associated with higher positive response rates to immunotherapy and better survival outcomes, indicating its potential to serve as a promising therapeutic and prognostic biomarker for cancer patients receiving immunotherapy.

TRIAL REGISTRATION: The protocol for this systematic review and meta-analysis has been registered on the PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ), with the registration number CRD42023470277.