Tumor-Infiltrating Lymphocytes, Crohn’s-Like Lymphoid Reaction, and Survival From Colorectal Cancer

• Published in: JNCI : Journal of the National Cancer Institute Vol. 108; no. 8
• Main Authors: Rozek, Laura S., Schmit, Stephanie L., Greenson, Joel K., Tomsho, Lynn P., Rennert, Hedy S., Rennert, Gad, Gruber, Stephen B.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.08.2016
• Subjects: Aged; Aged, 80 and over; Case-Control Studies; Cause of Death; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - mortality; Crohn Disease - immunology; Female; Humans; Immunity, Cellular; Israel - epidemiology; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - immunology; Male; Microsatellite Instability; Middle Aged; Prognosis; Proportional Hazards Models; Survival Rate
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djw027

While clinical outcomes from colorectal cancer (CRC) are influenced by stage at diagnosis and treatment, mounting evidence suggests that an enhanced lymphocytic reaction to a tumor may also be an informative prognostic indicator. The roles of intratumoral T lymphocyte infiltration (TIL), peritumoral Crohn's-like lymphoid reaction (CLR), microsatellite instability (MSI), and clinicopathological characteristics in survival from CRC were examined using 2369 incident CRCs from a population-based case-control study in northern Israel. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in multivariable models adjusted for age, sex, ethnicity, grade, stage, and MSI. All statistical tests were two-sided. Tumors with TIL/high-powered field (HPF) of 2 or greater were associated with a statistically significant increase in CRC-specific (P < .001) and overall survival (P < .001) compared with tumors with TIL/HPF of less than 2. Similarly, tumors with a prominent CLR experienced better CRC-specific (P < .001) and overall survival (P < .001) as compared with those with no response. High TILs (HR = 0.76, 95% CI = 0.64 to 0.89, P < .001) and a prominent CLR (HR = 0.71, 95% CI = 0.62 to 0.80, P < .001), but not MSI, were associated with a statistically significant reduction in all-cause mortality after adjustment for established prognostic factors. TILs and CLR are both prognostic indicators for CRC after adjusting for traditional prognostic indicators.