TY - JOUR
T1 - Exploratory study of macrophage polarization and spatial distribution in colorectal cancer liver metastasis
T2 - a pilot study
AU - Khanduri, Isha
AU - Maru, Dipen M.
AU - Parra, Edwin R.
N1 - Funding Information:
Support for the study was partially provided by the Translational Molecular Pathology Immunoprofiling Laboratory (TMP-IL) Moonshots Platform at the Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center.
Publisher Copyright:
Copyright © 2023 Khanduri, Maru and Parra.
PY - 2023
Y1 - 2023
N2 - Background: The liver is the most typical site of metastatic disease for patients with colorectal cancer (CRC), and up to half the patients with CRC will develop colorectal liver metastasis (CLM). Studying the tumor microenvironment, particularly macrophages and their spatial distribution, can give us critical insight into treatment. Methods: Ten CLMs (five treatment-naïve and five post–neoadjuvant chemotherapy) were stained with multiplex immunofluorescence panels against cytokeratins, CD68, Arg1, CD206, CD86, CD163, PD-L1, and MRP8-14. Densities of cell phenotypes and their spatial distribution in the tumor center and the normal liver–tumor interface were correlated with clinicopathological variables. Results: M2 macrophages were the predominant subtype in both the tumor center and the periphery, with a relatively higher density at the periphery. The larger tumors, more than 3.9 cm, were associated with higher densities of total CD68+ macrophages and CD68+CD163+ CD206neg and CD68+CD206+ CD163neg M2 macrophage subtypes. Total macrophages in the tumor periphery demonstrated significantly greater proximity to malignant cells than did those in the tumor center (p=0.0371). The presence of higher than median CD68+MRP8-14+CD86neg M1 macrophages in the tumor center was associated with poor overall survival (median 2.34 years) compared to cases with lower than median M1 macrophages at the tumor center (median 6.41 years) in univariate analysis. Conclusion: The dominant polarization of the M2 macrophage subtype could drive new therapeutic approaches in CLM patients.
AB - Background: The liver is the most typical site of metastatic disease for patients with colorectal cancer (CRC), and up to half the patients with CRC will develop colorectal liver metastasis (CLM). Studying the tumor microenvironment, particularly macrophages and their spatial distribution, can give us critical insight into treatment. Methods: Ten CLMs (five treatment-naïve and five post–neoadjuvant chemotherapy) were stained with multiplex immunofluorescence panels against cytokeratins, CD68, Arg1, CD206, CD86, CD163, PD-L1, and MRP8-14. Densities of cell phenotypes and their spatial distribution in the tumor center and the normal liver–tumor interface were correlated with clinicopathological variables. Results: M2 macrophages were the predominant subtype in both the tumor center and the periphery, with a relatively higher density at the periphery. The larger tumors, more than 3.9 cm, were associated with higher densities of total CD68+ macrophages and CD68+CD163+ CD206neg and CD68+CD206+ CD163neg M2 macrophage subtypes. Total macrophages in the tumor periphery demonstrated significantly greater proximity to malignant cells than did those in the tumor center (p=0.0371). The presence of higher than median CD68+MRP8-14+CD86neg M1 macrophages in the tumor center was associated with poor overall survival (median 2.34 years) compared to cases with lower than median M1 macrophages at the tumor center (median 6.41 years) in univariate analysis. Conclusion: The dominant polarization of the M2 macrophage subtype could drive new therapeutic approaches in CLM patients.
KW - colorectal cancer
KW - liver
KW - liver macrophages
KW - macrophages
KW - multiplex immunofluorescence
KW - spatial
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U2 - 10.3389/fimmu.2023.1223864
DO - 10.3389/fimmu.2023.1223864
M3 - Article
C2 - 37637998
AN - SCOPUS:85168655923
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1223864
ER -