The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Zhong, Xiaoming; Chen, Bin; Yang, Zhiwen

doi:10.1159/000486816

Cited by 109 publications

(94 citation statements)

References 55 publications

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“…The accentuation on the usage of M1/M2 ratio in prognosticating cancer is supported by the ambiguities concerning the sole densities of TAMs in patients' prognosis (29,30). For instance, although TAMs in general have negative effect on the gastric patients' prognosis in many studies (19,31,32), some studies showed opposing results (33)(34)(35).…”

Section: M1/m2 Ratio As the More Amenable Means Of Cancer Prognosticamentioning

confidence: 99%

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

et al. 2020

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Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

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Section: M1/m2 Ratio As the More Amenable Means Of Cancer Prognosticamentioning

confidence: 99%

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

et al. 2020

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“…Our study also included the assessment of macrophage density, at least two populations of macrophages with opposite immunological roles have been identified; as double edge swords, the M1 (classically activated) type with a proinflammatory antitumoral function and the M2 (alternatively activated) type with an immunosuppressive protumoral function [24,25]. It has been postulated that most of the tumor-associated macrophages belong to the M2 subtype [26].…”

Section: Discussionmentioning

confidence: 99%

Study of Tumor Microenvironment and Host Response in Colorectal Cancer: Immunohistochemical and Clinicopathological Approach

Raffalla

Helal

El-Latif

et al. 2019

Asian J Pharm Clin Res

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Objective: This study aimed to evaluate the immunohistochemical expression of forkhead boxP3 (Foxp3), CD8, CD68, and CD21 in stroma between tumor cells of colorectal cancer (CRC) patients and examines the relationship between these variables and clinicopathological parameter and patients’ prognosis. Methods: In this work, 50 cases of colorectal carcinomas were included and immunohistochemical evaluation of Foxp3, CD8, CD68, and CD21 in tumor tissue samples. Results: Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells and regulatory T cells as well as tumor-associated macrophages and follicular dendritic cells (FDCs) were studied in the stroma of the tumor using immunostaining technique for CD8, Foxp3, CD68, and CD21, respectively. Cases were followed up. CD8-positive cytotoxic T cells, Foxp3-positive regulatory T cells, and CD21 positive-FDCs were significantly more pronounced in early tumors and those with longer overall survival. On the other hand, CD68 positive macrophages were more encountered in late stage and metastatic tumors as well as tumors with shorter overall survival, but these results not reached the level of significance. Conclusion: We concluded that (TILs) and FDCs are conferring better prognosis in CRCs, they may act synergistically in stimulating a protective immune response in the tumor microenvironment that hinders tumor progression, while the role of tumor-associated macrophages in CRCs is still controversial and needs further studies.

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“…In colon cancer, the role of macrophages is controversial, with some authors claiming that a high infiltration is associated with better prognosis, while others report that their presence is associated with increased tumor progression-associated activities [5]. Our group has previously evidenced that macrophages induce gastric and colon cancer cell invasion, in a process partially mediated by secreted factors, and that the secretome of macrophages differs from that of macrophages co-cultured with cancer cells [6].…”

Section: Introductionmentioning

confidence: 95%

Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer

Martins

Oliveira

Cavadas

et al. 2020

Cancers

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In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage–cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures’ secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRPα expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome.

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The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Cited by 109 publications

References 55 publications

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Study of Tumor Microenvironment and Host Response in Colorectal Cancer: Immunohistochemical and Clinicopathological Approach

Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer

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