Tumor-Infiltrating Lymphocytes and Perforation in Colon Cancer Predict Positive Response to 5-Fluorouracil Chemotherapy

Abstract

Purpose: The major pathologic markers of prognosis in colorectal cancer include vascular invasion by tumor cells, invasion of adjacent lymph nodes, and perforation of the serosal wall. Recent work suggests that a high density of tumor-infiltrating lymphocytes (TIL) is associated with good outcome independently of these established prognostic markers. The aim of the present study was to investigate the prognostic significance of TILs and other routinely reported pathologic features in colon cancer, particularly in relation to the use of adjuvant chemotherapy. Experimental Design: Pathologic markers, disease-specific survival, and the use of adjuvant chemotherapy were recorded in a retrospective, population-based series of 1,156 stage III colon cancer patients with a median follow-up time of 52 months. Results: In patients treated by surgery alone (n = 851), markers with significant prognostic value included poor histologic grade,T4 stage, N2 nodal status, vascular invasion, and perforation, but not the presence of TILs. In patients treated with 5-fluorouracil^based chemotherapy (n = 305), TILs were associated with significantly improved survival [hazard ratio (HR), 0.52; 95 % confidence interval, 0.30-0.91; P = 0.02] and perforation with a trend for improved survival (HR, 0.67; 95% confidence interval, 0.27-1.05; P = 0.16). Patients withTILs or perforation seemed to gain more survival benefit from chemotherapy (HR, 0.22 and 0.21, respectively) than patients without these features (HR, 0.84 and 0.82, respectively). Conclusion: The apparent survival advantage from 5-fluorouracil associated with TILs and perforation requires confirmation in prospective studies. Because the presence of TILs reflects an adaptive immune response and perforation is associated with inflammatory response, these results suggest that there may be interactions between the immune system and chemotherapy leading to improved survival of colon cancer patients.

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

“…[24][25][26][27][28][29][30][31][32][33] As in this study, MSI tumors have previously been reported to have a higher degree of T-cell infiltration than MSS tumors. [35][36][37] Yet the potential confounding effect of MSI screening status on the prognostic importance of T-cell infiltration has been considered in only a minority of reports, of which most, 32,36,[39][40][41]46,53,54 but not all, 30,55 found that the better prognosis associated with dense T-cell infiltration was independent of MSI screening status.…”

“…Presence of peri-and intratumoral inflammatory cells has consistently been associated with a better prognosis in colorectal cancer. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Many of these reports have been based on routine hematoxylin and eosin stained tissue sections, but an increasing number of studies have used immunohistochemical markers such as the pan T-cell marker CD3. CD3 is a cell surface protein associated with the T-cell receptor.…”

Circulating Lymphocytes as Predictors of Sensitivity to Preoperative Chemoradiotherapy in Rectal Cancer Cases

“…Our results were consistent with some other scholars. Previous reports have suggested that a high number of tumor infiltrating lymphocytes was strongly associated with good outcomes in the patients with colorectal cancer (Galon et al, 2006;Morris et al, 2008;Laghi et al, 2009;Cañadas-Garre et al, 2012). A recent study conducted by Kitayama et al (2011) showed the association of a high lymphocyte ratio in peripheral blood before and during preoperative radiotherapy in the patients of rectal cancer with a complete pathological response, suggesting the lymphocyte-mediated immune response plays an important role in the eradication of tumor cells by preoperative radiotherapy.…”

Microenvironnement immunitaire et cancer

“…Il est par conséquent concevable que la nature de l'infiltration immunitaire au site tumoral (sa qualité, son intensité) puisse moduler la qualité de la réponse à ces thérapies. Le bénéfice de survie de patients atteints de CRC (colorectal cancer) ayant reçu une chimiothérapie à base de 5FU est grandement amélioré chez les patients qui présentent une forte infiltration de lymphocytes dans la tumeur (TIL) (p = 0,02) [32]. Étant donné que la présence de TIL reflète une réponse immunitaire adaptative, ces résul-tats suggèrent une interaction entre la réponse immunitaire et la chimiothérapie.…”