Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial

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• 作者：Devin C. Flaherty ; DO ; PhD^a ; Simon Lavotshkin ; MD^a ; John R. Jalas ; MD ; PhD^d ; Hitoe Torisu-Itakura ; MD ; PhD^b ; Daniel D. Kirchoff ; MD^a ; Myung S. Sim ; PhD^e ; Delphine J. Lee ; MD ; PhD^c ; Anton J. Bilchik ; MD ; PhD ; FACS^a ; ^e ; ^f ; ^{bilchika@jwci.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AJCC ; American Joint Committee on Cancer ; DFS ; disease-free survival ; IHC ; immunohistochemistry ; IM ; invasive margin ; MMR ; mismatch repair ; TC ; tumor center ; TIL ; tumor-infiltrating lymphocyte
• 刊名：Journal of the American College of Surgeons
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：223
• 期：1
• 页码：134-140
• 全文大小：855 K

文摘

Retrospective data indicate that immunoprofiling of T cell markers can be prognostic in colon cancer. Prospective T cell immunoprofiling of colon cancer has not been well defined for patients whose lymph nodes are ultrastaged.

Study Design

A prospective cohort was selected from patients enrolled in an ongoing phase II multicenter trial of nodal ultrastaging for colon cancer. Primary tumor specimens from 89 patients were analyzed by immunohistochemistry for the T cells CD3⁺, CD4⁺, CD8⁺, and FOXP3⁺. Lymphocyte populations were quantified with digital image analysis. Results were examined for their association with 5-year disease-free survival along with TNM stage and clinicopathologic variables.

Results

Longer disease-free survival was associated with higher CD3⁺ counts at the invasive margin (IM) (p = 0.005), higher CD8⁺ counts at the tumor center (TC) and IM (p = 0.002), a lower CD4⁺/CD8⁺ ratio at the TC+IM (p = 0.027), and a higher CD8⁺/FOXP3⁺ ratio at the TC+IM (p = 0.020). After multivariable analysis, CD8⁺ at the TC+IM (p = 0.002), the CD8⁺/FOXP3⁺ ratio at the TC+IM (p = 0.004), and the number of tumor-positive lymph nodes (p = 0.003) remained significant.

Conclusions

This is the first prospective demonstration of the prognostic utility of immunoprofiling in colon cancer after nodal ultrastaging. Staging based on tumor immunoprofile can augment TNM staging and provide targets for specific immunotherapies.