As is the case with most solid tumors, staging of colorectal cancer (CRC) uses histopathologic criteria of tumor invasion (T), spread to local lymph nodes (N), tumor metastases to distant organs (M) in the TNM classi?cation system click here to determine tumor staging and prognosis.1 An investigation based in France has demonstrated the efficacy of adding hisopathologic-based immune cell function to standard TNM system to further individualize CRC prognosis.2 Mlecnik and colleagues2 identified records of 599 patients with CRC who underwent primary resection at a hospital in Paris, France, between 1990 and 2004. All permanent section hematoxylin and eosin (HE) -stained slides were examined by blinded reviewers. Tissue microarray sections were evaluated by immunohistochemical (IHC) monoclonal antibodies against CD45RO, CD8, CD3, GZMB, and cytokeratin-8.2
- Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities.
- Sixty percent of patients with high densities of CD8 cytotoxic T-lymphocyte in?ltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor.
- In patients who did not relapse, the density of CD8 in?ltrates was inversely correlated with T stage.
- In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor.
- Univariate analysis showed that the immune score was signi?cantly associated with differences in disease-free, disease speci?c, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005).
- A ?nal stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001) compared with histopathologic features in predicting recurrence as well as survival.
The authors concluded that assessment of CD8 cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC-TNM staging.2
An adaptive immune system plays a major role in tumor eradication and disease outcome. The fact that the density of in?ltrating T cells can be quantitatively evaluated and that they are an independent predictor of prognosis2 suggests that the evaluation of CD8(+) and CD45RO(+) T-cell density should become part of the standard practice of evaluating CRC. It’s time to stop thinking about immune function as an issue solely related to hematological malignancies; instead, we need to move toward linking all the markers, immune and pathway, with physical characteristics of the tumor (TNM) to find an accurate way to determine the likelihood of recurrence. Then, working backward, that journey might lead to a cure…and prevention.
- Edge SB, Byrd DR, Compton CC, et al. (Eds). AJCC Cancer Staging Manual. 7th ed. 2010. New York: Springer. http://www.cancerstaging.org/products/ajccproducts.html
- Mlecnik B, Tosolini M, Kirilovsky A, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29: 610-618. doi:10.1200/JCO.2010.30.5425 Link to abstract http://jco.ascopubs.org/content/early/2011/01/18/JCO.2010.30.5425.short?rss=1