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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2018

01-08-2018 | Colorectal Cancer

Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer

Authors: Sumana Narayanan, MD, Tsutomu Kawaguchi, MD, PhD, Li Yan, PhD, Xuan Peng, MS, Qianya Qi, MS, Kazuaki Takabe, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 8/2018

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Abstract

Background

Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity.

Methods

Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA). CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition.

Results

High CYT was associated with high microsatellite instability (MSI-H), as well as high levels of activated memory CD4+T cells, gamma-delta T cells, and M1 macrophages. CYT-high CRC patients had improved overall survival (p = 0.019) and disease-free survival (p = 0.016) compared with CYT-low CRC patients, especially in TIL-positive tumors. Multivariate analysis demonstrated that CYT- high associates with improved survival independently after controlling for age, lymphovascular invasion, colonic location, microsatellite instability, and TIL positivity. The levels of immune checkpoint molecules (ICMs)—programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), T cell immunoglobulin and mucin domain 3 (TIM3), and indoleamine 2,3-dioxygenase 1 (IDO1)—correlated significantly with CYT (p < 0.0001); with improved survival in CYT-high and ICM-low patients, and poorer survival in ICM-high patients.

Conclusions

High CYT within CRC is associated with improved survival, likely due to increased immunity and cytolytic activity of T cells and M1 macrophages. High CYT is also associated with high expression of ICMs; thus, further studies to elucidate the role of CYT as a predictive biomarker of the efficacy of immune checkpoint blockade are warranted.
Appendix
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Metadata
Title
Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer
Authors
Sumana Narayanan, MD
Tsutomu Kawaguchi, MD, PhD
Li Yan, PhD
Xuan Peng, MS
Qianya Qi, MS
Kazuaki Takabe, MD, PhD, FACS
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6506-6

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