Clinical—Alimentary TractIntraepithelial Effector (CD3+)/Regulatory (FoxP3+) T-Cell Ratio Predicts a Clinical Outcome of Human Colon Carcinoma
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Patient Specimens
Surgically resected TNM stage II and III primary colon adenocarcinomas (n = 160) were analyzed from patients who participated in 5-fluorouracil (5-FU)–based adjuvant chemotherapy trials conducted by the Mayo Clinic and the North Central Cancer Treatment Group. Available paraffin-embedded tumor blocks from a nonrandom subset of study participants were used. Tumor histologic grade was categorized as follows: grade 1, well differentiated; grade 2, moderately differentiated; grade 3, poorly
Study Population
TNM stage II and III (136 [85%]) primary colon adenocarcinomas (n= 160) were analyzed from patients who participated in 5-FU–based adjuvant chemotherapy trials (see Materials and Methods). After 5 years of follow-up, 70.6% of patients were alive; at 8 years, 60.6% remained alive. Details of the study population are shown in Table 1.
FoxP3+ TILs in Human Colon Carcinomas
We analyzed Tregs, identified by FoxP3+ staining, and the adaptive immune marker CD3+ in colon carcinomas (Figure 1). Further evidence that FoxP3+ TILs were Tregs
Discussion
Tregs can suppress peripheral immune responses to tumor antigens, thus maintaining immunologic tolerance2, 9 and thereby contributing to tumor progression/metastasis.3, 12 We analyzed the expression and density of FoxP3+ TILs as a specific marker of Tregs5 and CD3+ TILs as an adaptive immune marker in human colon cancers. We found that FoxP3+ TILs were significantly enriched in primary colon cancers compared with autologous normal colonic mucosa. Similar to our results in tumor tissue, Tregs in
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Conflicts of interest The authors disclose no conflicts.
Funding Supported in part by National Cancer Institute grant CA104683-02 (to F.A.S.) and National Cancer Institute core grant CA15083 (to the Mayo Clinic Cancer Center).