Adding thymosin preparations to standard anticancer treatment raises certain circulating immune measures and performance status scores in people with colorectal cancer, but the overall evidence base remains too weak to justify routine clinical use, according to a new systematic review and meta-analysis of controlled studies.
The review, registered as CRD420261467566, was conducted by researchers at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine in Zhengzhou, China, and is set to appear in Frontiers in Oncology. Its objective was to evaluate the efficacy and safety of thymosin preparations added to the same background anticancer treatment in patients with colorectal cancer.
The research team searched nine bibliographic and trial-registration sources through 1 October 2026. They included both randomized controlled trials and nonrandomized studies with concurrent controls. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized trials and ROBINS-I for nonrandomized studies. Randomized trials provided the primary evidence, while nonrandomized studies were analyzed separately to avoid overstating their contribution.
In total, thirty studies involving 2,514 participants met the inclusion criteria: 25 randomized controlled trials covering 2,079 participants and five nonrandomized studies covering 435 participants. The analysts used Review Manager 5.4.1 to calculate risk ratios or mean differences with 95 percent confidence intervals, organized by treatment setting. Sensitivity analyses, GRADE assessment and an exploratory trial sequential analysis were used to probe the robustness and uncertainty of the findings.
The clearest signals emerged in postoperative randomized trials. Patients receiving thymosin had higher CD4 percentage (mean difference 6.33, 95 percent CI 4.89 to 7.76), higher CD4/CD8 ratio (mean difference 0.25, 95 percent CI 0.16 to 0.35) and higher NK-cell percentage (mean difference 6.41, 95 percent CI 3.72 to 9.11) than controls. By contrast, the findings for CD3 and CD8 percentages were inconclusive, meaning the confidence intervals did not allow a clear conclusion in either direction.
Karnofsky performance status was higher with thymosin in two postoperative randomized trials (mean difference 8.50, 95 percent CI 6.52 to 10.48) and in two advanced or mixed-stage trials (mean difference 4.35, 95 percent CI 1.90 to 6.80). The review authors noted, however, that source-reporting concerns affected the advanced or mixed-stage trials, so that estimate should be interpreted with particular caution.
Safety results were mixed and limited. Postoperative neutropenia was inconclusive in the single randomized trial that assessed it (risk ratio 0.91, 95 percent CI 0.82 to 1.01), while two nonrandomized studies reported a lower unadjusted risk of neutropenia with thymosin (risk ratio 0.65, 95 percent CI 0.51 to 0.83). Because the nonrandomized estimate is unadjusted and comes from a separate, lower-tier evidence stream, the review treated it as complementary rather than confirmatory. Comparable one-year survival evidence came from only one trial, leaving the effect on survival essentially unresolved.
Across all outcomes, the certainty of the evidence was judged low or very low under GRADE. The exploratory trial sequential analysis further underscored the uncertainty around the pooled estimates.
The review’s authors framed their conclusions carefully. They stated that the analysis identifies randomized-trial-based signals in circulating immune indices and performance status, and clarifies the contribution of nonrandomized evidence, with the aim of informing the selection of outcomes and treatment settings for future trials. They explicitly concluded that current evidence is insufficient to support routine clinical use of thymosin preparations in colorectal cancer.
The new analysis does not establish clinical benefit in survival or disease control; its most consistent findings concern laboratory immune markers and a functional status score. For patients and clinicians, the practical takeaway is that the immune-cell changes observed in postoperative trials have not yet been linked to demonstrated improvements in hard clinical outcomes, and the review's authors noted that these findings are intended to inform the selection of outcomes and treatment settings for future trials.
Subject of Research: A systematic review and meta-analysis of thymosin combined with anticancer therapy in colorectal cancer
Article Title: Efficacy and safety of thymosin combined with anticancer therapy for colorectal cancer: a systematic review and meta-analysis of controlled studies
Article References: Zhang, G., Zhou, Y., Sun, T., Chen, X., & Zheng, Y. (2026). Efficacy and safety of thymosin combined with anticancer therapy for colorectal cancer: a systematic review and meta-analysis of controlled studies. Frontiers in Oncology, 16, Article 1957041. https://doi.org/10.3389/fonc.2026.1957041
Image Credits: AI Generated
DOI: 10.3389/fonc.2026.1957041
Keywords: colorectal cancer, thymosin, thymalfasin, thymosin alpha 1, systematic review, meta-analysis, immunomodulation, CD4/CD8 ratio, NK cells, Karnofsky performance status, trial sequential analysis, GRADE
News Source: Nathaniel Bowman. (October 29, 2026). Thymosin added to colorectal cancer therapy shows immune signals but evidence falls short. Scienmag.
