Staging and the Immune Response to Colorectal Cancer

Alok A. Khorana, MD


March 28, 2011

Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction

Mlecnik B, Tosolini M, Kirilovsky A, et al
J Clin Oncol. 2011;29:610-618

Study Summary

Prognosis for patients with colorectal cancer relies primarily on tumor-node-metastases (TNM) staging, as it does for most solid tumors. However, the immune response to cancer may influence prognosis independent of the TNM stage.

Mlecnik and colleagues studied intratumoral immune infiltrates in the center of the tumor as well as at the invasive margin in 599 specimens of stage I through IV colorectal cancers. Early stage tumors (Tis/T1) were more likely to have high densities of CD8+ cytotoxic T-lymphocyte infiltrates (60%) than were T4 tumors (18%). In patients with recurrence, the number of CD8 cells was low, regardless of the T stage of the tumor.

In univariate analysis, the immune score was significantly associated with improved disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). In multivariate analysis, the immune score was more successful (HR, 0.64; P < .001) compared with histopathologic features in predicting recurrence as well as survival.


Predicting outcomes in patients with colorectal cancer is typically done using TNM staging. Within stages, however, there is wide variation in outcomes. Research efforts have focused primarily on identifying gene-expression profiles or specific genetic mutations predictive of disease-free or overall survival. In this important study, Mlecnik and coworkers demonstrate that the host immune response also plays an important role in determining prognosis. These findings have important implications for approaches that enhance the immune response to colorectal cancer to improve outcomes.



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