Tumour immune microenvironment prognostic factors in locally advanced rectal cancer, a systematic review.

Introduction: Understanding factors influencing individual survival outcomes following surgical resection of locally advanced (LARC) rectal cancer remains challenging. Novel biomarkers could show emerging promise in this setting. This study aimed to systematically review the literature on immune prognostic factors in LARC. Methods: The review protocol was preregistered on the PROSPERO database (CRD42023460541). Included studies were required to report overall survival and at least one immune prognostic factor for at least ten patients with LARC. Final searches of MEDLINE, EMBASE and Central were concluded on 8th September 2023. The risk of bias was assessed using the QUIPS tool. Results: 22 retrospective cohort studies involving 2,622 LARC patients were included in the review. We did not find any published data on immune prognostic factors in locally recurrent rectal cancer. Due to inconsistency of immune prognostic factor definitions and measurement methods, meta-analysis would not be meaningful. Instead, the results are presented descriptively. Risk of bias was concentrated in the participation, attrition, and confounding domains. Greater cytotoxic cell infiltration was associated with improved overall survival. There was inconsistent evidence of an association of PD-L1 expression and survival. M2 macrophage infiltration and homozygous germline FPR1 loss-of-function were associated with worse survival. Discussion: These findings support a role for both innate and acquired immune systems in mediating outcomes following surgery for LARC and suggest that further work into immunomodulation may show promise in improving LARC treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42023460541].