ArticleThe journal of pathology. Clinical research2022
A combination of stromal PD-L1 and tumoral nuclear β-catenin expression as an indicator of colorectal carcinoma progression and resistance to chemoradiotherapy in locally advanced rectal carcinoma.
Article in The journal of pathology. Clinical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Tumour immune microenvironment prognostic factors in locally advanced rectal cancer, a systematic review.Frontiers in oncology · 2025Pooled it
- Overcoming the Challenge: A Comprehensive Review of Neoadjuvant Treatment Resistance in Rectal Cancer.Journal of gastrointestinal cancer · 2025Review
- Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.Cell communication and signaling : CCS · 2024Review
- PD-L1 Expression in Paired Samples of Rectal Cancer.Cancers · 2024Article
- Article
- WNT/β-catenin regulatory roles on PD-(L)1 and immunotherapy responses.Clinical and experimental medicine · 2024Review
- Article
- Article
- Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review.World journal of clinical oncology · 2023Review
- Total neoadjuvant treatment and PD-1/PD-L1 checkpoint inhibitor in locally advanced rectal cancer.Frontiers in immunology · 2023Review
- Pathological Complete Response Following Neoadjuvant Tislelizumab Monotherapy in Treatment-Naive Locally Advanced, MMR-Deficient/MSI-High Ascending Colon Cancer: A Case Report.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Programmed cell death-1 (PD-1) and its ligand (PD-L1) are significant mediators of immune suppression in the tumor microenvironment. We focused on the immunological impact of PD-1/PD-L1 signaling during tumor progression in colorectal carcinoma (CRC) and its association with resistance to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal carcinoma (LAd-RC). Histopathological and immunohistochemical analyses of 100 CRC cases (including 34 RC) without NCRT and 109 NCRT-treated LAd-RC cases were performed. Membranous tumoral PD-L1 expression was identified in 9 of 100 (9%) CRC cases, including 1 of 34 (2.9%) RC cases, but PD-L1 immunopositivity was not associated with any clinicopathological factors, with the exception of deficient mismatch repair (dMMR) status. In contrast, stromal PD-L1+ immune cells, which frequently exhibited coexpression of PD-1 and CD8 markers, were significantly correlated with tumor vessel invasion, nuclear β-catenin+ tumor budding cancer stem cell (CSC)-like features, and unfavorable prognosis. In the LAd-RC cases, stromal CD8+ (but not PD-L1+) immune cell infiltration in pretreatment-biopsied samples was significantly and positively associated with therapeutic efficacy. After NCRT, tumoral PD-L1 expression was observed in only 2 of 83 (2.4%) tumors, independent of dMMR status, whereas high stromal PD-L1+ and tumoral nuclear β-catenin positivity were significantly linked to a poor response to NCRT and high tumor budding features. In addition, high stromal PD-L1 immunoreactivity was significantly associated with poorer overall survival. In conclusion, a combination of stromal PD-L1+ immune cells and nuclear β-catenin+ tumor budding may contribute to tumor progression in CRC and resistance to NCRT in LAd-RC, through formation of niche-like lesions that exhibit immune resistance and CSC properties.
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