High tumor mast cell density is associated with longer survival of colon cancer patients

Mehdawi, Lubna M.; Osman, Janina; Topi, Geriolda; Sjölander, Anita

doi:10.1080/0284186x.2016.1198493

Cited by 46 publications

(44 citation statements)

References 28 publications

(46 reference statements)

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“…Heterogeneous prognostic roles of MCs were found in different cancers . In CRC, several studies have investigated the relationship between MCs and prognosis with conflicting conclusions . Acikalin et al ., Gulubova and Vlaykova and Malfettone et al .…”

Section: Introductionmentioning

confidence: 99%

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

Mao

Feng

Zheng

et al. 2018

Intl Journal of Cancer

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The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, our study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stages I-IV was enrolled in our study. Consecutive patients (854) were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stages II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stages II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis.

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Section: Introductionmentioning

confidence: 99%

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

Mao

Feng

Zheng

et al. 2018

Intl Journal of Cancer

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“…It is possible that 5-LO derived products other than LTB 4 could have a direct promotional activity on intestinal tumors. Consistent with these observations, cystinyl leukotriene receptor 1 (CysLT1) deficient mice in the Apc Min/+ background were also shown to display reduced tumor burden [87]. …”

Section: Leukotriene B4 In Cancermentioning

confidence: 87%

The yin and yang of leukotriene B 4 mediated inflammation in cancer

Jala

Bodduluri

Satpathy

et al. 2017

Seminars in Immunology

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The high affinity leukotriene B4 receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB4/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB4/BLT1 axis enabling distinct outcomes toward tumor progression. In a mouse lung tumor model promoted by silicosis-induced inflammation, genetic deletion of BLT1 attenuated neutrophilic inflammation and tumor promotion. In contrast, in a spontaneous model of intestinal tumorigenesis, absence of BLT1 led to defective mucosal host response, altered microbiota and bacteria dependent colon tumor progression. Furthermore, BLT1 mediated CD8+ T cell recruitment was shown to be essential for initiating anti-tumor immunity in number of xenograft models and is critical for effective PD1 based immunotherapy. BLT2 mediated chemotherapy resistance, tumor promotion and metastasis are also discussed. This new information points to a paradigm shift in our understanding of the LTB4 pathways in cancer.

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“…Furthermore, IL-5, which can be produced by mast cells and eosinophils, has been shown to promote eosinophil infiltration into tumors and suppress tumor metastasis [51]. We have previously shown that an increased mast cell density has been associated with a better prognosis in colorectal cancer patients, and an increased mast cell number was seen in tumors of AOM/DSS Cysltr1 −/− mice [52]. Taken together, the increased mast cell number and increased IL-5 serum levels indicate a more favorable outcome for Cysltr1 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer

et al. 2017

Self Cite

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Cysteinyl leukotriene receptor 1 (CysLT1R) has been shown to be up-regulated in the adenocarcinomas of colorectal cancer patients, which is associated with a poor prognosis. In a spontaneous model of colon cancer, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1−/−) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R in the induced azoxymethane/dextran sulfate sodium (AOM/DSS) model of colitis-associated colon cancer. We found that AOM/DSS female mice with a global disruption of the Cysltr1 gene (Cysltr1−/−) had a higher relative body weight, a more normal weight/length colon ratio and smaller-sized colonic polyps compared to AOM/DSS wild-type counterparts. The Cysltr1−/− colonic polyps exhibited low-grade dysplasia, while wild-type polyps had an adenoma-like phenotype. The Cysltr1−/− colonic polyps exhibited significant decreases in nuclear β-catenin and COX-2 protein expression, while the normal crypts surrounding the polyps exhibited increased Mucin 2 expression. Furthermore, Cysltr1−/− mice exhibited an overall reduction in inflammation, with a significant decrease in proinflammatory cytokines, polyp 5-LOX expression and infiltration of CD45 leukocytes and F4/80 macrophages. In conclusion, the present genetic approach in an AOM/DSS model further supports an important role for CysLT1R in colon tumorigenesis.

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High tumor mast cell density is associated with longer survival of colon cancer patients

Cited by 46 publications

References 28 publications

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

The yin and yang of leukotriene B 4 mediated inflammation in cancer

Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer

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