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B7H3 Immune Checkpoint Overexpression Is Associated with Decreased Complete Response Rates to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Authors :
Sebastian Curcean
Raluca Maria Hendea
Rares Buiga
Alexandru Tipcu
Andra Curcean
Catalin Vlad
Zsolt Fekete
Alina-Simona Muntean
Daniela Martin
Alexandru Irimie
Source :
Diagnostics, Vol 14, Iss 18, p 2023 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Background and Objectives: Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune checkpoint protein, plays a role in tumor progression and resistance to therapy, and correlates with poor prognosis in various cancers, including colorectal cancer. This study aims to evaluate the expression of B7H3 in LARC and its impact on overall complete response (oCR) rates to neoadjuvant therapy. Methods: A retrospective study was conducted on 60 patients with LARC who received neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision (TME). B7H3 expression was assessed using immunohistochemistry on surgical specimens. Expression levels were categorized as high or low based on a composite score, and their association with oCR rates was analyzed. Results: High B7H3 expression was observed in 60% of patients, with 73.5% showing expression in more than 50% of tumor cells. Patients who achieved oCR had significantly lower B7H3 expression compared to those with residual disease (p < 0.001). No nuclear expression of B7H3 was detected. No significant correlation was found between B7H3 expression and other clinicopathological variables, except for a higher likelihood of non-restorative surgery in patients with elevated B7H3 levels (p = 0.049). Mucinous adenocarcinoma had high expression of B7H3. Conclusions: Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC.

Details

Language :
English
ISSN :
20754418
Volume :
14
Issue :
18
Database :
Directory of Open Access Journals
Journal :
Diagnostics
Publication Type :
Academic Journal
Accession number :
edsdoj.feac7b8ead7a4bc7aa87a66c0607c3e7
Document Type :
article
Full Text :
https://doi.org/10.3390/diagnostics14182023