Tumor-associated macrophages (TAMs) have a unique favorable effect on the prognosis of colorectal cancer (CRC), although their association with stage-specific outcomes remains unclear. We assessed the densities of CD68+ and CD163+ TAMs at the invasive front of resected CRC stage III CRC from 236 patients, 165 of whom received post-surgical FOLFOX treatment, and their relationship with disease-free survival (DFS). Associations between macrophage mRNAs and clinical outcome were investigated in silico in 59 stage III CRC and FOLFOX-treated patients from The Cancer Genome Atlas (TCGA). Biological interactions of SW480 and HT29 cells and macrophages with FOLFOX were tested in co-culture models. Low TAM densities were associated with shorter DFS among patients receiving FOLFOX (CD68+, p = 0.0001; CD163+, p = 0.0008) but not among those who were untreated. By multivariate Cox analysis, only low TAM (CD68+, p = 0.001; CD163+, p = 0.002) and nodal status (CD68+, p = 0.009; CD163+, p = 0.007) maintained an independent predictive value. In the TCGA cohort, high CD68 mRNA levels were associated with better outcome (p = 0.02). Macrophages enhanced FOLFOX cytotoxicity on CRC cells (p < 0.01), and drugs oriented macrophage polarization from M2- to M1-phenotype. Low TAM densities identify stage III CRC patients at higher risk of recurrence after adjuvant therapy, and macrophages can augment the chemo-sensitivity of micro-metastases.

Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer / Cavalleri, T.; Greco, L.; Rubbino, F.; Hamada, T.; Quaranta, M.; Grizzi, F.; Sauta, E.; Craviotto, V.; Bossi, P.; Vetrano, S.; Rimassa, L.; Torri, V.; Bellazzi, R.; Mantovani, A.; Ogino, S.; Malesci, A.; Laghi, L.. - In: THE JOURNAL OF PATHOLOGY. CLINICAL RESEARCH. - ISSN 2056-4538. - 8:4(2022), pp. 307-312. [10.1002/cjp2.267]

Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer

Laghi L.
2022-01-01

Abstract

Tumor-associated macrophages (TAMs) have a unique favorable effect on the prognosis of colorectal cancer (CRC), although their association with stage-specific outcomes remains unclear. We assessed the densities of CD68+ and CD163+ TAMs at the invasive front of resected CRC stage III CRC from 236 patients, 165 of whom received post-surgical FOLFOX treatment, and their relationship with disease-free survival (DFS). Associations between macrophage mRNAs and clinical outcome were investigated in silico in 59 stage III CRC and FOLFOX-treated patients from The Cancer Genome Atlas (TCGA). Biological interactions of SW480 and HT29 cells and macrophages with FOLFOX were tested in co-culture models. Low TAM densities were associated with shorter DFS among patients receiving FOLFOX (CD68+, p = 0.0001; CD163+, p = 0.0008) but not among those who were untreated. By multivariate Cox analysis, only low TAM (CD68+, p = 0.001; CD163+, p = 0.002) and nodal status (CD68+, p = 0.009; CD163+, p = 0.007) maintained an independent predictive value. In the TCGA cohort, high CD68 mRNA levels were associated with better outcome (p = 0.02). Macrophages enhanced FOLFOX cytotoxicity on CRC cells (p < 0.01), and drugs oriented macrophage polarization from M2- to M1-phenotype. Low TAM densities identify stage III CRC patients at higher risk of recurrence after adjuvant therapy, and macrophages can augment the chemo-sensitivity of micro-metastases.
Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer / Cavalleri, T.; Greco, L.; Rubbino, F.; Hamada, T.; Quaranta, M.; Grizzi, F.; Sauta, E.; Craviotto, V.; Bossi, P.; Vetrano, S.; Rimassa, L.; Torri, V.; Bellazzi, R.; Mantovani, A.; Ogino, S.; Malesci, A.; Laghi, L.. - In: THE JOURNAL OF PATHOLOGY. CLINICAL RESEARCH. - ISSN 2056-4538. - 8:4(2022), pp. 307-312. [10.1002/cjp2.267]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2926612
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