Tumour‐associated macrophages correlate with microvascular bed extension in colorectal cancer patients

Marech, Ilaria; Ammendola, Michele; Sacco, Rosario; Sammarco, Giuseppe; Zuccalà, Valeria; Zizzo, Nicola; Leporini, Christian; Luposella, Maria; Patruno, Rosa; Filippelli, Gianfranco; Russo, Emilio; Porcelli, Mariangela; Gadaleta, Cosmo Damiano; Sarro, Giovambattista De; Ranieri, Girolamo

doi:10.1111/jcmm.12826

Cited by 34 publications

(29 citation statements)

References 61 publications

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“…In this study, it was found that there was a significant correlation between macrophage infiltration and microvascular density in a series of tumors from 76 CRC patients. Therefore, TAMs could be used as a marker for angiogenesis-mediated CRC [50]. …”

Section: The Role Of Tams On Tumor Angiogenesis Crc Growthmentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Zhong¹,

Chen²,

Yang³

2018

Cell Physiol Biochem

109

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Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.

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Section: The Role Of Tams On Tumor Angiogenesis Crc Growthmentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Zhong¹,

Chen²,

Yang³

2018

Cell Physiol Biochem

109

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“…To this regard, it is important to underline that MCs can stimulate neovascularization releasing mainly tryptase stored in their secretory granules [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

Ammendola

Sacco

Zuccalà

et al. 2016

IJMS

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Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2–3N2–3M0 (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

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“…Conflicting data exist whether macrophages and which subtype contribute to CRC progression. [13][14][15][16][17] Lymphocytes also provide defense functions in order to maintain the integrity of the epithelial barrier within the healthy intestinal mucosa. 18 These cells have an activated yet resting manifestation 19 and the memory phenotype is enriched among T cells.…”

Section: Introductionmentioning

confidence: 99%

Immunological differences between colorectal cancer and normal mucosa uncover a prognostically relevant immune cell profile

et al. 2018

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T cells in colorectal cancer (CRC) are associated with improved survival. However, checkpoint immunotherapies antagonizing the suppression of these cells are ineffective in the great majority of patients. To better understand the immune cell regulation in CRC, we compared tumor-associated T lymphocytes and macrophages to the immune cell infiltrate of normal mucosa. Human colorectal tumor specimen and tumor-distant normal mucosa tissues of the same patients were collected. Phenotypes and functionality of tissue-derived T cells and macrophages were characterized using immunohistochemistry, RNA in situ hybridization, and multiparameter flow cytometry. CRC contained significantly higher numbers of potentially immunosuppressive CD39 and Helios-expressing regulatory T cells in comparison to normal mucosa. Surprisingly, we found a concomitant increase of pro-inflammatory IFNγ -producing T cells. PD-L1+ stromal cells were decreased in the tumor tissue. Macrophages in the tumor compared to tumor-distant normal tissue appear to have an altered phenotype, identified by HLA-DR, CD14, CX3CR1, and CD64, and tolerogenic CD206+ macrophages are quantitatively reduced. The prognostic effect of these observed differences between distant mucosa and tumor tissue on the overall survival was examined using gene expression data of 298 CRC patients. The combined gene expression of increased FOXP3, IFNγ, CD14, and decreased CD206 correlated with a poor prognosis in CRC patients. These data reveal that the CRC microenvironment promotes the coexistence of seemingly antagonistic suppressive and pro-inflammatory immune responses and might provide an explanation why a blockade of the PD1/PD-L1 axis is ineffective in CRC. This should be taken into account when designing novel treatment strategies.

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Tumour‐associated macrophages correlate with microvascular bed extension in colorectal cancer patients

Cited by 34 publications

References 61 publications

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

Immunological differences between colorectal cancer and normal mucosa uncover a prognostically relevant immune cell profile

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