Low Intratumoral Mast Cells Are Associated With a Higher Risk of Prostate Cancer Recurrence

Hempel, Heidi; Cuka, Nathan; Kulaç, İbrahim; Barber, John R.; Cornish, Toby C.; Platz, Elizabeth A.; Marzo, Angelo M. De; Sfanos, Karen S.

doi:10.1002/pros.23280

Cited by 50 publications

(66 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In tissue samples from specimens containing prostate cancer, there are increased mast cell numbers in areas of prostate cancer versus benign prostate tissues, and mast cells numbers are higher in density in lower Gleason grade than in higher Gleason grade cancers [14,[19][20][21][22][23]. We and others have reported that high intra-tumoral mast cell numbers are associated with favorable prognosis [14,19,23]. The opposite association exists for extra-tumoral mast cells, where high mast cell numbers are associated with worse prognosis.…”

Section: Introductionmentioning

confidence: 75%

“…The opposite association exists for extra-tumoral mast cells, where high mast cell numbers are associated with worse prognosis. We previously analyzed mast cell density in relation to race and both biochemical recurrence (PSA progression) and the development of metastases after radical prostatectomy [14,24]. Our findings highlight an important predictive role for high numbers of benign tissue (extra-tumoral) mast cell numbers in association with a higher risk of both biochemical recurrence and metastases in both African-American and European-American men [14,24].…”

Section: Introductionmentioning

confidence: 86%

“…Furthermore, mast cells may play differential, and possibly even opposing roles, in tumor initiation and progression. For example, while the majority of human cancer studies report increased numbers of mast cells in the tumor microenvironment and their potential association with tumor initiation [12], many studies report that decreased numbers or loss of mast cells within the tumor associates with a worse prognosis [13][14][15][16]. The significance of MCT versus MCTC mast cell subtypes in relation to cancer are even less clear.…”

Section: Introductionmentioning

confidence: 99%

“…We previously analyzed mast cell density in relation to race and both biochemical recurrence (PSA progression) and the development of metastases after radical prostatectomy [14,24]. Our findings highlight an important predictive role for high numbers of benign tissue (extra-tumoral) mast cell numbers in association with a higher risk of both biochemical recurrence and metastases in both African-American and European-American men [14,24]. Previous studies have identified both MCT and MCTC mast cells in the prostate of men with prostate cancer [25,26]; however, mast cell subtypes have not been previously examined in relation to race or prostate cancer prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differential Mast Cell Phenotypes in Benign versus Cancer Tissues and Prostate Cancer Oncologic Outcomes

Sullivan

maynard

Heaphy

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

We previously reported that high numbers of mast cells in benign (extra-tumoral) regions of the prostate are associated with worse outcomes after radical prostatectomy including biochemical recurrence and the development of metastases. Herein, on a cohort of 384 men, we performed mast cell subtyping and report that higher minimum number of the tryptase-only (MCT) subset of extra-tumoral mast cells is associated with increased risk of biochemical recurrence (comparing highest to lowest tertiles: HR 2.20, 95% CI 1.32-3.65; P-trend 0.004), metastases (HR 3.60, 95% CI 1.77-7.36; P-trend 0.001), and death from prostate cancer (HR 2.96, 95% CI 1.23-7.08; P-trend 0.02). RNAsequencing of benign versus cancer tissue mast cells revealed differential expression of additional site-specific genes. We demonstrate that genes more highly expressed in tumor-infiltrating mast cells, such as CXCR4 and TFE3, represent an altered tumor microenvironment. C-kit variants were also differentially expressed in benign versus cancer tissue mast cells, with C-kit variant 1 (GNNK+) mast cells identified as more prevalent in extra-tumoral regions of the prostate. Finally, using an established mouse model, we found that mast cells do not infiltrate Hi-Myc tumors, providing a model to specifically examine the role of extra-tumoral mast cells in tumorigenesis. Hi-Myc mice crossed to mast cell knockout (Wsh) mice and aged to one year revealed a higher degree of pre-invasive lesions and invasive cancer in wildtype mice versus heterozygous and knockout mice. This suggests a dosage effect where higher numbers of extra-tumoral mast cells resulted in higher cancer invasion. Overall, our studies provide further evidence for a role of extra-tumoral mast cells in driving adverse prostate cancer outcomes.

show abstract

Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential Mast Cell Phenotypes in Benign versus Cancer Tissues and Prostate Cancer Oncologic Outcomes

Sullivan

maynard

Heaphy

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hempel et al (66) showed a protective role of intratumoral mastocytes connecting a low number of intratumoral mast cells with a higher risk of prostate cancer recurrence (66). …”

Section: Prostate Cancer and Inflammationmentioning

confidence: 99%

Inflammation in Prostatic Hyperplasia and Carcinoma—Basic Scientific Approach

et al. 2017

View full text Add to dashboard Cite

Chronic inflammation is associated with both benign conditions and cancer. Likewise, inflammatory cells are quite common in benign prostatic hyperplasia (BPH) and prostatic tissue harboring cancer. Triggers that activate inflammatory pathways in the prostate remain a subject of argument and are likely to be multifactorial, some of these being bacterial antigens, different chemical irritations, and metabolic disorders. Acute and chronic inflammation in prostate leads to accumulation of immunocompetent cells, mainly T lymphocytes and macrophages, but also neutrophils, eosinophils, and mast cells, depending on the type of offending agent. Inflammatory processes activate hyperproliferative programs resulting in nodules seen in BPH, but are also important in creating suitable microenvironment for cancer growth and progression. Inflammatory cells have mostly been shown to have a protumoral effect such as tumor-associated macrophages, but some cell types such as mast cells have antitumoral effects. This review outlines the recent findings and theories supporting the role of inflammatory responses as drivers of both benign and malignant epithelial processes in the prostate gland.

show abstract

Development and validation of a leukocyte‐associated immunoglobulin‐like receptor‐1 prognostic signature for lower‐grade gliomas

Fang

et al. 2022

Cancer Medicine

View full text Add to dashboard Cite

Objective Leukocyte‐associated immunoglobulin‐like receptor‐1 (LAIR‐1), is an immunosuppressive receptor, widely expressed by immune cells, but the part of LAIR‐1 in glioma progression remains unclear. The purpose of this study was to explore the relationship between LAIR‐1 expression and the development of lower‐grade glioma (LGG) using publicly available data sets. Methods We took advantage of The Cancer Genome Atlas (TCGA) to analyze the expression of LAIR‐1 in patients with LGG. Second, Kaplan‐Meier methods and univariate and multivariate Cox regression analyses were used to examine the clinical significance of LAIR‐1 expression in combination with CGGA databases, and then receiver operating characteristic curve analysis was used to verify the prognostic utility of LAIR‐1. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were used to explore the function of LAIR‐1. Analysis of the correlation with immune infiltration was conducted using the ESTIMATE algorithm and single sample gene set enrichment analysis. Results Our results showed that LAIR‐1 expression to be positively correlated with malignant clinicopathologic features of LGG. Univariate analysis and multivariate analysis revealed that overexpression of LAIR‐1 was correlated with a worse prognosis in patients. A nomogram model combining LAIR‐1 was more useful in guiding clinical diagnosis, and functional enrichment analysis showed that malignant development of glioma was closely affiliated with the tumor immune microenvironment. Conclusion These results indicate that LAIR 1 is a latent marker for determining the prognosis of LGG patients. LAIR 1 may also participate a critical part in TIME of LGG by regulating the infiltration of immune cells, suggesting that LAIR 1 might be used as a therapeutic target to regulate the antitumor immune response.

show abstract

Low Intratumoral Mast Cells Are Associated With a Higher Risk of Prostate Cancer Recurrence

Abstract: Our results suggest that intratumoral mast cells may be protective against prostate cancer recurrence and could potentially serve as a prognostic biomarker after prostatectomy. Prostate 77: 412-424, 2017. © 2016 Wiley Periodicals, Inc.

Cited by 50 publications

References 40 publications

Differential Mast Cell Phenotypes in Benign versus Cancer Tissues and Prostate Cancer Oncologic Outcomes

Differential Mast Cell Phenotypes in Benign versus Cancer Tissues and Prostate Cancer Oncologic Outcomes

Inflammation in Prostatic Hyperplasia and Carcinoma—Basic Scientific Approach

Development and validation of a leukocyte‐associated immunoglobulin‐like receptor‐1 prognostic signature for lower‐grade gliomas

Contact Info

Product

Resources

About