Clinical impact of tumor‐infiltrating lymphocytes for survival in stage II colon cancer

Abstract

BACKGROUND:The most reliable prognostic factor in colon cancer is the TNM classification. The objective of this study was to assess and compare the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage II colon cancer. METHODS: Immunohistochemistry was used to assess the density of TILs that were positive for cluster of differentiation 3 (CD3) (T-cell coreceptor), CD45 isoform RO (CD45RO) (protein tyrosine phosphatase), nuclear transcription factor forkhead box P3 (FOXP3), and CD25 (a type I transmembrane protein) according to tumor site (intraepithelial and stromal) in samples from 87 patients who had stage II colon cancer. These variables were evaluated for their association with histopathologic features along with overall survival (OS) and disease-free survival (DFS). RESULTS: Intraepithelial CD3-posititve (CD3þ), CD45ROþ, CD25þ, and FOXP3þ TILs were associated significantly with better DFS (P ¼ .049, P ¼ .009, P ¼ .013, and P ¼ .001, respectively). The estimated 5-year OS rates for patients who had high-density CD45ROþ and FOXP3þ expression was 100% for both compared with 79.2% and 78.8% for patients who had low-density CD45ROþ and FOXP3þ expression (P ¼ .017 and P ¼ .040, respectively). A significant prognostic factor for both OS and DFS was high-density stromal CD45ROþ lymphocytic infiltration (OS: P ¼ .031; relative risk [RR], 0.134; 95% confidence interval [CI], 0.015-1.164; DFS: P ¼ .013; RR, 0.198; 95% CI, 0.055-0.710); whereas intraepithelial FOXP3þ expression was an independent prognostic factor for DFS (P ¼ .032; RR, 0.108; 95% CI, 0.014-0.821). CONCLUSIONS: FOXP3þ and CD45ROþ TILs demonstrated independent prognostic significance for survival in the current investigation. These results may help to improve the prognostication of early stage colon cancer. Cancer 2010;116:5188-99.

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

“…A prognostic marker indicating risk of recurrence and cancer-related death is of particular clinical interest in stage II colorectal cancer, since high-risk patients within this subgroup may potentially benefit from adjuvant chemotherapy, which today is not routinely administered. Together with other stage-stratified results, 21,24,40,41,47,55,58 Figure 2 Cancer-specific survival in colorectal cancer patients with low (3-4), intermediate (5)(6), and high (7-12) total CD3 score (log rank Po0.0001). our findings justify the use of tumor infiltrating T cells as a prognostic marker in stage II colorectal cancer.…”

“…58 T-cell infiltration is not homogeneous in colorectal cancer, and attention has therefore also been focused on the predictive values of T cells in different tumor compartments. 32,33,37,[42][43][44][45][46][47] In this study, the separate measurements of T-cell infiltration in the tumor front, center, and intraepithelial compartment were closely correlated and were all positively associated with cancer-specific survival. Two previous studies found that a high total lymphocyte score, similar to that used in this study, more accurately predicted cancer-specific survival compared with any single score separately.…”

“…32,42 Furthermore, T-cell infiltration can be assessed in various locations within the tumor, such as the tumor front, tumor center, and the intraepithelial compartment, but few studies have evaluated these separately. 32,33,37,[42][43][44][45][46][47] Although a beneficial effect on survival has generally been observed with higher degrees of infiltrating T cells, the prognostic value has varied in reports depending on the T-cell marker used, the compartment evaluated, and the confounders considered.…”

Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer

“…Immunohistochemical studies in CRC have been directed to the detection of the origin of metastatic colonic lesions and CRC prognosis with discordant results (44,45). We did not find any publication focused on the possible value of immunohistochemistry for the assessment of tumor multicentricity risk, which is the principal topic of our research.…”

Surface profiles of live colorectal cancer cells and tumor infiltrating lymphocytes from surgical samples correspond to prognostic categories

“…Hierarchical cluster analysis of the 11 CRC and TIL antigens produced similar groups of patients that were separated into three categories (relapse-free, systemic relapse, and cancer-specific death), supporting the hypothesis that surface antigen profiles on CRC cells and TIL yield prognostic information. (Wagner et al, 2001;Shelley et al, 2002;Lee et al, 2010).…”