It is possible that tumour-infiltrating granulocytes promote tumour progression

Liu, Huanran; Ubukata, Hideyuki; Takemura, Akihiro; Motohashi, Gyou; Nishimura, Motoi; Satani, Tetsuro; Hong, Jian-Wei; Katano, Motonobu; Nakada, Ichiro; Saniabadi, Abbi R.; Tabuchi, Takafumi

doi:10.3892/or_00000402

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…26 Other experimental tumor models suggest that neutrophils contribute to tumor growth, metastasis, and immunosuppression by producing angiogenic factors, by facilitating tumor cell extravasation, and by suppressing T-lymphocyte cytokine synthesis. [7][8][9][10] Our results, along with the study on renal cell cancer, 19 bronchioloalveolar carcinoma, 27 and another on gastric carcinoma 28 indicate the existence of an association between tumor-infiltrating neutrophils and poor prognosis, which suggests that tumor-infiltrating neutrophils may have a protumoral function. Furthermore, we have previously reported an association between pretreatment elevated neutrophil counts in blood and poor prognosis in metastatic renal cell carcinoma and metastatic melanoma.…”

Section: Discussionsupporting

confidence: 51%

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

Jensen

Schmidt

Møller

et al. 2011

Cancer

221

181

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BACKGROUND: Tumor cell and host immune cell interaction plays a key role in carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer and believed to be an important mediator of tumor-induced immunosuppression. This paper aims to describe the prognostic impact of neutrophil and dendritic cell infiltration in primary melanoma and the association of this infiltration with activated STAT3 (pSTAT3) in primary melanoma cells. METHODS: Formalin-fixed, paraffin-embedded primary melanomas from 186 stage-I/II melanoma patients surgically resected from 1997 to 2000. Infiltrating neutrophils (CD66b), dendritic cells (CD123þ and DC-LAMPþ), T-lymphocytes (CD8) and pSTAT3 melanoma cell expression were studied by immunohistochemistry and evaluated as present or absent. DC-LAMPþ cell infiltration was evaluated as absent/few versus dense. Study endpoints: relapse-free survival, melanoma-specific, and overall survival. RESULTS: The median observation time was 12.2 years (range, 10.4-14.2 years). Fifty-one deaths were observed of which 38 (20%) were melanoma-specific. In a multivariate Cox proportional hazards model including ulceration and melanoma thickness, neutrophil and CD123þ dendritic cell infiltration were independently associated with poor prognosis (CD66b: hazard ratio [HR] ¼ 3.13; 95% confidence interval [CI], 1.43-6.83; P ¼ .004; CD123: HR ¼ 2.45; 95% CI, 1.22-4.92; P ¼ .012). The association between melanoma cell pSTAT3 expression and immune infiltration (neutrophils and CD123þ cells) was strong. pSTAT3 expression, CD8 and DC-LAMP infiltration were not independently associated with poor prognosis. CONCLUSIONS: Neutrophil infiltration and CD123þ dendritic cell infiltration in primary melanoma are independently associated with poor prognosis. Melanoma cell expression of pSTAT3 is strongly associated with the surrounding immune infiltrate. Cancer 2012;118:2476-

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Section: Discussionsupporting

confidence: 51%

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

Jensen

Schmidt

Møller

et al. 2011

Cancer

221

181

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“…The granulocyte/lymphocyte ratio was associated with abnormal levels of G-CSF (more than 50 % of the cancer patients) and TIGs were a risk factor for lymph node metastasis in colorectal carcinoma [178]. Similarly, in gastric carcinoma, TIGs were associated with tumor stage and shorter survival time [373].…”

Section: Prognostic Values Of Neutrophils and Other Myeloid Subtypes mentioning

confidence: 98%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

324

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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“…We previously reported that the neutrophil/lymphocyte ratio (NLR) in peripheral blood was a good indicator of tumor progression, and excessive production of neutrophils may be unfavorable to anti‐cancer immunity 3, 4. These results led us to consider that normal anti‐cancer immunity is necessary for the normal balance of immunocompetent cells and cytokines.…”

Section: Introductionmentioning

confidence: 99%