Background: Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. Methods: We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. Results: CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p= 0.02) and paracancerous tissues (p< 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p= 0.01), FOXP3+ regulatory T-cells (p< 0.01), and CD20+ B-cells (p< 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p< 0.01) and CD20+ (p< 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p< 0.038) and reduced CD8+ infiltrates (p= 0.02). Conclusion: In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.
背景：慢性炎症是结直肠癌（CRC）发展的重要因素，尤其在结肠炎相关结直肠癌（CAC）中。已知T细胞耗竭会影响炎症性肠病（IBD）的进展以及IBD患者的抗肿瘤免疫。本研究旨在识别CAC患者独特的免疫浸润特征。方法：我们研究了20例CAC患者和20例散发性结直肠癌（sCRC）患者，两组患者在肿瘤分期、分级和部位上进行了匹配。通过免疫组织化学染色检测两组患者肿瘤组织及无瘤黏膜中多种T细胞标志物（CD3、CD4、CD8和FOXP3）、T细胞耗竭标志物（TOX和TIGIT）、B细胞标志物（CD20）以及中性粒细胞标志物（CD66b）。采用肿瘤免疫基质定量算法评估免疫浸润细胞。结果：在肿瘤组织（p=0.02）和癌旁组织（p<0.01）中，CAC患者的TOX+细胞浸润均显著低于sCRC患者。与左侧CAC相比，右侧CAC的TOX+细胞（p=0.01）、FOXP3+调节性T细胞（p<0.01）和CD20+B细胞（p<0.01）浸润增加。在sCRC中，较高肿瘤分期（III期和IV期）的TIGIT+细胞浸润显著低于I期和II期。在CAC中，较高的CD3+（p<0.01）和CD20+（p<0.01）细胞浸润与总生存期改善相关。在sCRC中，生存期改善与TIGIT+细胞减少（p<0.038）和CD8+细胞浸润降低（p=0.02）相关。结论：在CAC中，较高的CD3+和CD20+细胞浸润与生存期改善相关，而sCRC中未发现此关联。研究揭示了TIGIT和TOX表达的显著差异，强调了CAC与sCRC之间的区别。T细胞耗竭在CAC发展中似乎扮演着不同的角色。
肿瘤(癌症)患者之家