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In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer
Journal of Clinical Oncology, 10/30/09

Pagès F et al. – Many patients who present with early-stage colorectal cancer (International Union Against Cancer TNM stages I and II) are nevertheless at high risk of relapse. We hypothesized that intratumoral immune reaction could influence their prognosis. The combined analysis of CD8+ plus CD45RO+ cells in specific tumor regions could provide a useful criterion for the prediction of tumor recurrence and survival in patients with early-stage colorectal cancer.

Methods

Intratumoral immune reaction investigated in 29 tumors by large-scale real-time polymerase chain reaction
Cytotoxic (CD8) and memory (CD45RO) T cells quantified by immunohistochemical analyses of tissue microarrays from center (CT) and invasive margin (IM) of 602 tumors from 2 independent cohorts
Results correlated with tumor recurrence and patient survival

Results

Patients with strong infiltration of CD45RO+ cells in tumor exhibited increased expression of T-helper 1 and cytotoxicity-related genes
Densities of CD45RO+ and CD8+ cells in tumor regions (CT/IM) classified patients into 4 distinct prognostic groups based on presence of high density of each marker in each tumor region
4 groups associated with dramatic differences in disease-free, disease-specific, and overall survival
5 years after diagnosis, only 4.8% (95% CI, 0.6% to 8.8%) of patients with high densities of CD8+ plus CD45RO+ cells had tumor recurrence, and 86.2% (CI, 79.4% to 93.6%) survived
Tumor recurred in 75% (95% CI, 17% to 92.5%) of patients with low densities of these cells, and only 27.5% (95% CI, 10.5% to 72%) survived
Multivariate analyses showed that immune criteria had independent effects on rates of complete remission and survival

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