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. 2016 May 12;108(8):djw027.
doi: 10.1093/jnci/djw027. Print 2016 Aug.

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

Laura S Rozek  1 , Stephanie L Schmit  1 , Joel K Greenson  1 , Lynn P Tomsho  1 , Hedy S Rennert  1 , Gad Rennert  1 , Stephen B Gruber  1
Affiliations

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

Laura S Rozek et al. J Natl Cancer Inst. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: TILs and CLR are both prognostic indicators for CRC after adjusting for traditional prognostic indicators.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier colorectal cancer (CRC)–specific survival curves by (A) microsatellite instability (MSI) status (Nsolid = 296, events = 85; Ndashed = 1675, events = 664), (B) T lymphocyte infiltration (TIL) status (Nsolid = 539, events = 139; Ndashed = 1449, events = 619), and (C) Crohn’s-like lymphoid reaction (CLR) (Nsolid = 692, events = 215; Ndashed = 799, events = 385). MSI log-rank χ2 = 10.9, P < .001. TIL log-rank χ2 = 46.9, P < .001. CLR log-rank χ2 = 50.8, P < .001. All statistical tests were two-sided. CLR = Crohn’s-like reaction; MSI-H = microsatellite instability–high; MSS/MSI-L = microsatellite-stable/microsatellite-low; TIL = tumor infiltrating lymphocytes per high powered field.
Figure 2.
Figure 2.
Kaplan-Meier colorectal cancer (CRC)–specific survival curves by (A) T lymphocyte infiltration (TIL) and microsatellite instability (MSI) status (Nblack = 362, events = 95; Nblue = 152, events = 39; Ngreen = 120, events = 40; Nred = 1250, events = 541); (B) Crohn’s-like lymphoid reaction (CLR) and MSI status (Nblack = 547, events = 175; Nblue = 110, events = 30; Ngreen = 85, events = 23; Nred = 682, events = 346); (C) TIL status and stage (Npink = 91, events = 4; Npurple = 116, events = 19; Nmaroon = 203, events = 40; Norange = 443, events = 129; Nblue = 96, events = 39; Ngreen = 344, events = 180; Nblack = 41, events = 36; Nred = 231, events = 208); and (D) CLR and stage (Npink = 102, events = 8; Npurple = 87, events = 13; Nmaroon = 303, events = 61; Norange = 273, events = 86; Nblue = 155, events = 59; Ngreen = 231, events = 127; Nblack = 77, events = 67; Nred = 141, events = 131). All statistical tests were two-sided. CLR = Crohn’s-like reaction; MSI-H = microsatellite instability–high; MSS/MSI-L = microsatellite-stable/microsatellite-low; TIL = tumor infiltrating lymphocytes per high powered field.
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