Tumor infiltration by T lymphocytes expressing chemokine receptor 7 (CCR7) is predictive of favorable outcome in patients with advanced colorectal carcinoma

Abstract

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% CI: 24.5-51.4) vs. 20 months (95% CI: 11.4-28.5); HR=0.48 (95% CI: 0.24-0.96); P=0.03] and prolonged progression-free survival [PFS; high vs. low T ccr7 score: median 12 months (95% CI: 7.7-16.2) vs. 7 months (95% CI: 5.2-8.7); HR = 0.54 (95% CI: 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% CI: 20.8-49.1) vs. 17 months (95% CI: 4.6-29.3); HR=0.32 (95% CI: 0.12-0.87); P=0.02 and median PFS=11 months (95% CI: 9.4-12.5) vs. 5 months (95% CI: 2.2-7.7); HR=0.43 (95% CI: 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. ©2011 AACR.