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

Abstract

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. 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. 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]. 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.