IMMUNOREACT 0: Biopsy‐based immune biomarkers as predictors of response to neoadjuvant therapy for rectal cancer—A systematic review and meta‐analysis

BACKGROUND: The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta‐analysis to estimate their predictive significance. METHODS: A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included. RESULTS: Seventeen studies reporting sufficient data met the inclusion criteria for meta‐analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD‐L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD‐L1 and CTLA‐4 were not correlated to the treatment response. CONCLUSION: This meta‐analysis indicated that high‐density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.