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Meta-Analysis
. 2023 Sep;12(17):17878-17890.
doi: 10.1002/cam4.6423. Epub 2023 Aug 3.

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

Astghik Stepanyan  1 , Matteo Fassan  2   3 , Gaya Spolverato  1 , Ignazio Castagliuolo  4 , Melania Scarpa  5 , Marco Scarpa  1 ; IMMUNOREACT Study Group
Collaborators, Affiliations
Meta-Analysis

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

Astghik Stepanyan et al. Cancer Med. 2023 Sep.

Abstract

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.

Keywords: lymphocytes; marker; neoadjuvant therapy; pathological complete response; rectal cancer.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Prisma flow diagram of the search strategy.
FIGURE 2
FIGURE 2
Forest plot representing the correlation between high level of CD3+ TILs and response to NT.
FIGURE 3
FIGURE 3
Forest plots representing the correlation between response to NT and high level of (A) total CD4+ TILs, (B) CD4+ intraepithelial TILs.
FIGURE 4
FIGURE 4
Forest plots representing the correlation between response to NT and high level of (A) total CD8+ TILs, (B) CD8+ stromal TILs, (C) CD8+ intraepithelial TILs.
FIGURE 5
FIGURE 5
Forest plots representing the correlation between response to NT and high level of unfractionated PD‐L1.
FIGURE 6
FIGURE 6
Immune markers in rectal tumor patients receiving neoadjuvant therapy associated with good or poor response to therapy.
See this image and copyright information in PMC

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