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Meta-Analysis
. 2020 Feb 25;10(1):3360.
doi: 10.1038/s41598-020-60255-4.

The Prognostic Implications of Tumor Infiltrating Lymphocytes in Colorectal Cancer: A Systematic Review and Meta-Analysis

Gregory E Idos  1 , Janet Kwok  2 , Nirupama Bonthala  3 , Lynn Kysh  4 , Stephen B Gruber  5 , Chenxu Qu  2
Affiliations
Meta-Analysis

The Prognostic Implications of Tumor Infiltrating Lymphocytes in Colorectal Cancer: A Systematic Review and Meta-Analysis

Gregory E Idos et al. Sci Rep. .

Abstract

Tumor-infiltrating lymphocytes (TILs) are an important histopathologic feature of colorectal cancer that confer prognostic information. Previous clinical and epidemiologic studies have found that the presence and quantification of tumor-infiltrating lymphocytes are significantly associated with disease-specific and overall survival in colorectal cancer. We performed a systematic review and meta-analysis, establishing pooled estimates for survival outcomes based on the presence of TILs in colon cancer. PubMed (Medline), Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to April 2017. Studies were included, in which the prognostic significance of intratumoral tumor infiltrating lymphocytes, as well as subsets of CD3, CD8, FOXP3, CD45R0 lymphocytes, were determined within the solid tumor center, the invasive margin, and tumor stroma. Random-effects models were calculated to estimated summary effects using hazard ratios. Forty-three relevant studies describing 21,015 patients were included in our meta-analysis. The results demonstrate that high levels of generalized TILS as compared to low levels had an improved overall survival (OS) with a HR of 0.65 (p = <0.01). In addition, histologically localized CD3+ T-cells at the tumor center were significantly associated with better disease-free survival (HR = 0.46, 95% CI 0.36-0.61, p = 0.05), and CD3 + cells at the invasive margin were associated with improved disease-free survival (HR = 0.57, 95% CI 0.38-0.86, p = 0.05). CD8+ T-cells at the tumor center had statistically significant prognostic value on cancer-specific survival and overall survival with HRs of 0.65 (p = 0.02) and 0.71 (p < 0.01), respectively. Lastly, FOXP3+ T-cells at the tumor center were associated with improved prognosis for cancer-specific survival (HR = 0.65, p < 0.01) and overall survival (HR = 0.70, p < 0.01). These findings suggest that TILs and specific TIL subsets serve as prognostic biomarkers for colorectal cancer.

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Conflict of interest statement

Dr. Gregory Idos has received research funding from Myriad Genetics. Dr. Stephen Gruber has consulted for Myriad Genetics and Fulgent Therapeutics. He has equity ownership interest in Brogent International LLC. Miss. Kysh, Dr. Bonthala, Dr. Kwok, and Dr. Qu declare no potential conflict of interest.

Figures

Figure 1
Figure 1
TIL Meta-Analysis Flow Diagram.
Figure 2
Figure 2
Forest plots of random effects between levels of generalized inflammatory infiltrate and survival. (A) The effect of generalized tumor infiltrate on cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS). (B) Funnel plots of meta-analyses to assess the association between TILs and survival.
Figure 3
Figure 3
Forest plots of random effects between levels of CD3+ T-cell infiltrate and Survival. The effect of CD3+ T-cells in the (A) tumor center (B) invasive margin (C) stroma on cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS).
Figure 4
Figure 4
Forest plots of random effects between levels of CD8+ T-cell infiltrate and Survival. The effect of CD8+ T-cells in the (A) tumor center (B) invasive margin (C) stroma on cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS).
Figure 5
Figure 5
Forest plots of random effects between levels of FOXP3+ T-cell infiltrate and Survival. The effect of FOXP3+ T-cells in the (A) tumor center (B) invasive margin (C) stroma on cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS).
Figure 6
Figure 6
Forest plots of random effects between levels of CD45R0+ T-cell infiltrate and Survival. The effect of CD45R0+ T-cells in the (A) tumor center (B) invasive margin (C) stroma on cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS).
See this image and copyright information in PMC

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