Tissue-Infiltrating Lymphocytes as a Predictive Factor for Recurrence in Patients with Curatively Resected Colon Cancer: A Propensity Score Matching Analysis

Abstract

Background: In patients with colorectal cancer, the rate of recurrence increases as the histologic stage progresses. However, the prediction of recurrence in individual patients is difficult. Many studies have reported on the relation between outcomes and tissue-infiltrating lymphocytes (TILs). The aim of our study was to clarify the relation between TILs and oncologic outcomes in patients with colon cancer using propensity score matching analysis.

Methods: The study group comprised 513 patients with colon cancer who received curative resection. By using propensity score matching for sex, age, tumor location, T stage, N stage, histologic type, and adjuvant therapy as conventional prognostic factors, 61 patients with recurrence and 61 patients with no recurrence were selected. Hematoxylin-eosin staining and immunohistochemical staining using CD3, CD8, CD4, and FoxP3 were performed for lymphocytes in the primary tissue. The results were evaluated separately in the whole tumor, the central part, and the invasive margin.

Results: The median follow-up period was 53 months. Among the 513 patients, 70 had recurrence and 443 had no recurrence. In the comparison of outcomes between the 61 patients with recurrence and the 61 patients with no recurrence, univariate analysis showed that the disease-free survival rate was significantly higher among the patients with positive TILs in the whole tumor and in the invasive margin (p = 0.016 and p = 0.012, respectively) and with CD8+ cells in the central part (p = 0.039) than among those with negative results. A multivariate analysis showed that TILs in the invasive margin (hazard ratio 1.81; 95% confidence interval, 1.03-3.05; p = 0.037) and CD8+ cell density in the central part (hazard ratio 1.76; 95% confidence interval, 1.07-2.93; p = 0.023) were prognostic factors that were independent from conventional prognostic factors.

Conclusions: In patients with curatively resected colon cancer, TILs in the invasive margin and CD8+ cell density in the central part may be prognostic factors suggesting host antitumor immune response.

Keywords: Colon cancer; Prognostic factor; Tissue-infiltrating lymphocytes.

Fig. 1

aAbsence or a few CD8+ cells infiltrating the central part (grade 0). bMild infiltration of CD8+ cells in the central part (grade 1). cModerate infiltration of CD8+ cells in the central part (grade 2). dStrong infiltration of CD8+ cells in the central part (grade 3).

Fig. 2

Examples of stained sections showing different patterns of T-cell infiltration in the microenvironment of colon tumors. aMinor T-cell infiltration in the invasive margin. bStrong infiltration of T cells in the invasive margin. cA few CD8+ cells infiltrating the central part. dStrong infiltration of CD8+ cells in the central part.