Tumor Infiltration by T Lymphocytes Expressing Chemokine Receptor 7 (CCR7) Is Predictive of Favorable Outcome in Patients with Advanced Colorectal Carcinoma

Purpose: An efficient adaptive immunity is critical for a longer survival in cancer. We investigated the prognostic value of tumor infiltration by CD8(+) T cells expressing the chemokine-receptor-7 (T-ccr7) and the correlation between tumor infiltration by T-ccr7 and regulatory CD4(+)FoxP3(+) T cells (T-reg) in 76 metastatic colorectal cancer (mCRC) patients enrolled in a phase III trial. Experimental Design: T-ccr7 and T-reg cell infiltration in tumor samples was quantified by immunohistochemistry. The correlation among T-ccr7, T-reg tumor infiltration, and patients' outcome was evaluated. Results: High T-ccr7 tumor infiltration was predictive of prolonged OS [high vs. low T-ccr7 score: median 38 months (95% Cl: 24.5-51.4) vs. 20 months (95% Cl: 11.4-28.5); HR = 0.48 (95% Cl: 0.24-0.96); P=0.03] and prolonged progression-free survival [ITS; high vs. low T-ccr7 score: median 12 months (95% Cl: 7.7-16.2) vs. 7 months (95% Cl: 5.2-8.7); HR = 0.54 (95% Cl: 0.28-1.01); P = 0.01] after front-line chemotherapy. Regression analysis did not show correlation between T-ccr7 and T-reg infiltration levels. However, the cluster of patients showing concomitant high infiltration by both T-ccr7 and T-reg disclosed a favorable outcome [double high vs. double low tumor infiltration score: median OS = 35 months (95% Cl: 20.8-49.1) vs. 17 months (95% Cl: 4.6-29.3); HR = 0.32(95% Cl: 0.12-0.87); P = 0.02 and median PFS = 11 months (95% CI: 9.4-12.5) vs. 5 months (95% Cl: 2.2-7.7); HR = 0.43 (95% Cl: 0.17-1.06); P = 0.01]. Conclusions: High T-ccr7 tumor infiltration score is a favorable prognostic factor for mCRC. Our findings underline the relevance of microenvironment-related immunologic events for patient outcome. Clin Cancer Res; 18(3); 850-7. (C) 2011 AACR.