Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome

Marwan Fakih, Ching Ouyang, Chongkai Wang, Travis Yiwey Tu, Maricel C. Gozo, May Cho, Marvin Sy, Jeffrey A. Longmate, Peter P. Lee

Research output: Contribution to journalArticle

Abstract

The prognostic value of immune cell infiltration within the tumor microenvironment (TME) has been extensively investigated via histological and genomic approaches. Based on the positive prognostic value of T cell infiltration, Immunoscore has been developed and validated for predicting risk of recurrence for colorectal cancer (CRC). Also, association between a consensus T helper 1 (Th-1) immune response and favorable clinical outcomes has been observed across multiple cancer types. Here, we reanalyzed public genomic data sets from The Cancer Genome Atlas (TCGA) and NCBI Gene Expression Omnibus (NCBI-GEO) and performed multispectral immunohistochemistry (IHC) on a cohort of colorectal tumors. We identified and characterized a risk group, representing approximately 10% of CRC patients, with high intratumoral CD8+ T cell infiltration, but poor prognosis. These tumors included both microsatellite instable (MSI) and stable (MSS) phenotypes and had a high density of tumor-associated macrophages (TAMs) that expressed CD274 (programmed death-ligand 1 [PD-L1]), TGF-β activation, and an immune overdrive signature characterized by the overexpression of immune response and checkpoint genes. Our findings illustrate that CRC patients may have poor prognosis despite high CD8+ T cell infiltration and provide CD274 as a simple biomarker for identifying these patients.

Original languageEnglish (US)
Pages (from-to)4464-4476
Number of pages13
JournalJournal of Clinical Investigation
Volume129
Issue number10
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

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Colorectal Neoplasms
T-Lymphocytes
Neoplasms
Tumor Microenvironment
Atlases
Microsatellite Repeats
Biomarkers
Immunohistochemistry
Macrophages
Genome
Ligands
Phenotype
Gene Expression
Recurrence
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fakih, M., Ouyang, C., Wang, C., Yiwey Tu, T., Gozo, M. C., Cho, M., ... Lee, P. P. (2019). Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. Journal of Clinical Investigation, 129(10), 4464-4476. https://doi.org/10.1172/JCI127046

Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. / Fakih, Marwan; Ouyang, Ching; Wang, Chongkai; Yiwey Tu, Travis; Gozo, Maricel C.; Cho, May; Sy, Marvin; Longmate, Jeffrey A.; Lee, Peter P.

In: Journal of Clinical Investigation, Vol. 129, No. 10, 01.10.2019, p. 4464-4476.

Research output: Contribution to journalArticle

Fakih, M, Ouyang, C, Wang, C, Yiwey Tu, T, Gozo, MC, Cho, M, Sy, M, Longmate, JA & Lee, PP 2019, 'Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome', Journal of Clinical Investigation, vol. 129, no. 10, pp. 4464-4476. https://doi.org/10.1172/JCI127046
Fakih, Marwan ; Ouyang, Ching ; Wang, Chongkai ; Yiwey Tu, Travis ; Gozo, Maricel C. ; Cho, May ; Sy, Marvin ; Longmate, Jeffrey A. ; Lee, Peter P. / Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. In: Journal of Clinical Investigation. 2019 ; Vol. 129, No. 10. pp. 4464-4476.
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