Naohiko Akimoto, MD, PhD, Atsushi Tatsuguchi, MD, PhD, Aitoshi Hoshimoto, MD, PhD, Yuka Shimazu, MD, Ryosuke Inoue, MD, Takayoshi Nishimoto, MD, Jun Omori, MD, PhD, Ryuji Ohashi, MD, PhD, Masanori Atsukawa, MD, PhD Nippon Medical School, Tokyo, Tokyo, Japan Introduction: Advanced adenomas are important precursors of colorectal cancer and highlight the need for early endoscopic treatment. Meanwhile, the global incidence of early-onset colorectal cancer (diagnosed before age 50) is rising, necessitating improved prevention and management strategies. Although molecular and pathological characteristics have been studied, the immunological landscape—particularly the role of T cell subtypes—remains insufficiently characterized, especially in endoscopically resected specimens. This study examined the relationship between densities of T cell subtypes (CD3+, CD4+, CD8+, FOXP3+) and clinicopathological features, focusing on advanced adenomas (defined as adenomas ≥10 mm, with a villous component, or high-grade dysplasia including pTis) and tumors diagnosed before age 50. Methods: We analyzed 279 colorectal lesions from 163 patients (98 advanced adenomas and 191 early-onset tumors) using a molecular pathology database. All lesions were resected via cold snare polypectomy, EMR, or ESD at Nippon Medical School Hospital between February 2017 and January 2020. FFPE specimens underwent immunohistochemical staining for CD3, CD4, CD8, and FOXP3. T cell densities were quantified in tumor, stromal, and normal mucosa using 200x magnified images (BZX800, KEYENCE). One to five fields per lesion were analyzed (median: five). Stromal and normal region analysis was limited to specimens of sufficient size. Clinicopathological data were reviewed retrospectively. Statistical methods included chi-square, Spearman’s rank correlation, Mann–Whitney U, and Kruskal–Wallis tests. Results: Tumor locations: distal colon (48%), proximal colon (39%), rectum (13%). Compared with non-advanced adenoma, advanced adenoma showed significantly lower CD3+, CD4+, and CD8+ T cell densities (all P < 0.001). Similarly, early-onset tumors had significantly lower CD3+, CD4+, and CD8+ densities than later-onset tumors (all P < 0.001). T cell densities decreased with increasing tumor size (all P < 0.001). CD3+, CD8+, and FOXP3+ distributions varied significantly by tumor location; however, within early-onset tumors, no significant location-based differences were found. Discussion: Endoscopic specimens suggest that T cell-mediated immune responses vary with age at onset, tumor size, histology, and location. These findings emphasize the need to define immunologically distinct subsets of high-risk tumors that may warrant intensified post-resection surveillance.
Disclosures: Naohiko Akimoto indicated no relevant financial relationships. Atsushi Tatsuguchi indicated no relevant financial relationships. Aitoshi Hoshimoto indicated no relevant financial relationships. Yuka Shimazu indicated no relevant financial relationships. Ryosuke Inoue indicated no relevant financial relationships. Takayoshi Nishimoto indicated no relevant financial relationships. Jun Omori indicated no relevant financial relationships. Ryuji Ohashi indicated no relevant financial relationships. Masanori Atsukawa indicated no relevant financial relationships.
Naohiko Akimoto, MD, PhD, Atsushi Tatsuguchi, MD, PhD, Aitoshi Hoshimoto, MD, PhD, Yuka Shimazu, MD, Ryosuke Inoue, MD, Takayoshi Nishimoto, MD, Jun Omori, MD, PhD, Ryuji Ohashi, MD, PhD, Masanori Atsukawa, MD, PhD. P4572 - Comparative T Cell Immune Landscapes Including Advanced Adenoma and Early-Onset Colorectal Tumor: Analysis of Endoscopic Resection Samples, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
