Prognostic implications of TAMs in colorectal cancer hepatic metastases.

Authors

null

Matthew Reilley

The University of Texas MD Anderson Cancer Center, Houston, TX

Matthew Reilley , Sreyashi Basu , Riham Katkhuda , Nicolle Patterson , Tenghui Chen , Jorge M Blando , David Menter , Dipen M. Maru , James Patrick Allison , Scott Kopetz , Padmanee Sharma , Michael J. Overman

Organizations

The University of Texas MD Anderson Cancer Center, Houston, TX, MD Anderson Cancer Center, Houston, TX

Research Funding

Other

Background: A limited understanding of the immune microenvironment of mismatch repair-proficient metastatic colorectal cancer (mCRC) impedes efforts to develop effective immunotherapy treatments for the majority of CRC patients. Liver metastatic disease is common and associated with poor outcomes. While T-cell infiltration of liver metastases positively correlates with survival, most mCRC patients do not benefit from checkpoint-blockade therapy. Tissue associated macrophages (TAMs) have been associated with an immune suppressive environment, but their prognostic role in mCRC is largely unknown. Methods: Comprehensive analysis of gene expression and immunohistochemistry (IHC) in 25 microsatellite stable (MSS) untreated liver metastatectomy (LM) specimens was performed. Clinical outcomes including recurrence, immunologic data, and tumor microsatellite status were evaluated and correlated. Results: Principal component analysis of immune and cancer pathway related genes were performed and compared with recurrence status. All samples were confirmed MSS. There were distinct differences in gene expression between patients who remained disease free and those who recurred. Among immune related genes CXCL5, IRF4, IL6R, TNF, CTLA4, ICOS, and ARG1 were relatively over-expressed in non-recurrent tumors, while PPARG, AIRE, and EPCAM were over-expressed in recurrent tumors (FDR 0.2, p < 0.05). Cibersort analysis predicts a significantly higher number of M2 versus M1 macrophages regardless of recurrence status (p < 0.05), with an approximate M1:M2 ratio of 1:2 and a higher total number of M1/M2 macrophages in tumors that recur. On IHC, an average of 29% of cells per sample expressed macrophage marker CD68. Relatively fewer CD3, CD4, and CD8 T cells were observed with average infiltration rates of 7.4%, 3.6%, and 2.6% respectively. Conclusions: CRC liver metastases demonstrate evidence of a large TAM population with significant M2 component and a smaller T cell population. A greater number of TAMs appear to correlate with recurrence, while a more immunogenic phenotype correlates with lower recurrence risk.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer–Advanced Disease

Citation

J Clin Oncol 35, 2017 (suppl; abstr 3574)

DOI

10.1200/JCO.2017.35.15_suppl.3574

Abstract #

3574

Poster Bd #

197

Abstract Disclosures

Similar Abstracts

First Author: Katherine Emilie Rhoades Smith

First Author: Colin William Steele