Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer

SIMPLE SUMMARY: Chronic inflammation plays a significant role in colorectal cancer (CRC) development, particularly in colitis-associated CRC (CAC). This study examined immune infiltration patterns in CAC patients compared to sporadic CRC (sCRC) patients and their impact on prognosis. Twenty CAC and twenty sCRC patients, matched by tumor characteristics, were analyzed. Immunohistochemistry targeted various immune markers, including T-cell and B-cell markers, in tumor and adjacent mucosal tissues. The results revealed differences between CAC and sCRC in T-cell exhaustion markers (TOX and TIGIT) and immune cell infiltration. High CD3+ and CD20+ cell levels correlated with improved survival in CAC but not in sCRC. This study highlighted distinct immune profiles in CAC and sCRC, suggesting that T-cell exhaustion might play a different role in CAC development than in sCRC. Understanding these immune differences could impact treatment strategies and prognosis for CAC patients. ABSTRACT: 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.