Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels; Nordsmark, Marianne; Lundbeck, Finn; Maase, Hans von der

doi:10.1200/jco.2008.18.9498

Cited by 385 publications

(333 citation statements)

References 50 publications

Supporting

Mentioning

298

Contrasting

Unclassified

Order By: Relevance

“…30,31 Nevertheless, neutrophils represent an independent prognostic marker in a broad variety of neoplasias. For instance, a high number of intratumoral neutrophils in localized 32 as well as metastatic 32 renal cell carcinoma, correlates with a negative prognosis. 32 Similarly, infiltration of gliomas by neutrophils has been correlated with higher tumor stages 33 and it is apparently also associated with more aggressive types of pancreas carcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, a high number of intratumoral neutrophils in localized 32 as well as metastatic 32 renal cell carcinoma, correlates with a negative prognosis. 32 Similarly, infiltration of gliomas by neutrophils has been correlated with higher tumor stages 33 and it is apparently also associated with more aggressive types of pancreas carcinomas. 34 In accordance, tumor infiltrating neutrophils represent a highly potent therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

Andzinski

Lienenklaus

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

The importance of neutrophils in tumor immune surveillance, invasive growth and angiogenesis becomes increasingly clear. Many of neutrophil activities are controlled by endogenous IFN-b. Here, we provide evidence that endogenous IFN-b is regulating the apoptosis of pro-angiogenic tumor infiltrating neutrophils by influencing both, the extrinsic as well as the intrinsic apoptosis pathways. Accordingly, the life span of tumor associated neutrophils (TANs) is remarkably prolonged in tumor bearing Ifnb1 2/2 mice compared to wild type controls. Lower expression of Fas, reactive oxygen species, active Caspase 3 and 9, as well as a change in expression pattern of proapoptotic and antiapoptotic members of the Bcl-2 family and the major apoptosome constituent Apaf-1 is observed under such conditions. In line with inhibition of apoptosis and the prolonged neutrophil survival, in the absence of endogenous IFN-b, a strong enhancement of G-CSF expression and PI3 Kinase phosphorylation is detected. These data explain the increased longevity of tumor infiltrating neutrophils and the accumulation of such cells in tumors. Taken together, our findings add to the important role of Type I IFN in immune surveillance against cancer.Neutrophilic granulocytes are the most abundant white blood cells in circulation, that are released from the bone marrow as terminally differentiated, nondividing cells. 1 Besides their role in immunity, neutrophils strongly influence growth, metastasis, 2 angiogenesis 3,4 and immune surveillance 5 of tumors. In contrast to cells of the adaptive immune system, neutrophils need no activation to acquire an effector phenotype. In accordance with their pleiotropic function, neutrophils are equipped with a large array of effector molecules like proteolytic enzymes, antimicrobial proteins/peptides and are able to produce reactive oxygen species. 6 Due to their potential toxicity against host tissue, the life span of such cells is strictly regulated. 7 In the absence of noxious or inflammatory stimuli, neutrophils are removed from circulation by apoptosis shortly after their emigration from the bone marrow. However, several proinflammatory cytokines have been shown to influence the longevity of neutrophils. 8 Type I interferons (IFNs) were first identified as factors responsible for the phenomenon of viral interference. In the meantime, they are recognized to influence a broad variety of biological processes, such as maintenance of cellular homeostasis, 9 hematopoiesis, 10 lymphocyte development 11 and apoptosis of dendritic 12 or CD4 1 T cells 13 besides their role in infections. In addition, Type I IFNs display strong antitumor effects by exhibiting direct antiproliferative and proapoptotic effects on tumor cells 14 as well as supporting systemic immunity against tumor targets by up-regulation of MHC class I expression, enhancement of cytotoxic T cell responses and activation of natural killer cells and macrophages. 15 Nevertheless, the mechanism of how Type I IFNs contribute to immune surveillance against tumo...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

Andzinski

Lienenklaus

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…In addition, increased neutrophil counts were associated with increased mortality in patients with bronchoalveolar cancer, renal cell carcinoma and malignant melanoma (Wislez et al, 2003;Fridlender and Albelda, 2012). Also, increased neutrophil counts were reported to be a strong and independent prognostic factor for overall survival, recurrence and cancer-specific survival in patients with renal cancer and head and neck tumors (Jensen et al, 2009;Trellakis et al, 2011). Glial tumor grade was also higher in the presence of neutrophil infiltration (Fossati et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Subtypes of White Blood Cells in Patients with Prostate Cancer or Benign Prostatic Hyperplasia and Healthy Individuals

Cihan¹,

Arslan²,

Ergül³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: This study aimed to evaluate the baseline white blood cell (WBC), neutrophil, lymphocyte, monocyte, basophil, eosinophil count, total prostate-specific antigen (TPSA), free PSA (FPSA) level, neutrophilto-lymphocyte and neutrophil-to-monocyte ratios among patients with prostate cancer and benign prostatic hyperplasia (BPH), as well as healthy individuals. Materials and Methods: 2005-2012 laboratory files of 160 patients with prostate cancer at Kayseri Training and Research Hospital, Oncology Outpatient Clinic, 285 patients who were pathologically diagnosed with BPH in Urology Outpatient Clinic and 200 healthy individuals who were admitted to Internal Medicine Outpatient Clinic were retrospectively analyzed. Baseline WBC, neutrophil, lymphocyte, monocyte, basophil, eosinophil count, TPSA, FPSA level, neutrophil-to-lymphocyte ratio and neutrophil-to-monocyte ratio were recorded and compared across groups. Results: Patients with prostate cancer had a lower lymphocyte level compared to the patients with BPH and healthy controls (p<0.001). The mean monocyte count, leukocyte-to-monocyte ratio, and leukocyte-to-lymphocyte ratio were higher in patients with prostate cancer, but without significance. The mean WBC and leukocyte count were lower in patients with prostate cancer, but again without statistical significance (p=0.130). The mean TPSA and FPSA were 39.4 and 5.67, respectively in patients with prostate cancer, while they were 5.78 and 1.28 in patients with BPH. There was a significant difference in the mean TPSA and FPSA levels between the patient groups (p<0.001). Conclusions: Our study results showed that patients with prostate cancer had a lower level of lymphocytes, neutrophils and WBCs and a higher level of monocytes with a significant difference in lymphocyte count, compared to healthy controls. We suggest that lymphocyte count may be used in combination with other parameters in the diagnosis of prostate cancer, thanks to its ease of assessment.

show abstract

“…[390] Metastatic renal cell carcinoma Patients with elevated neutrophil count (>6,500 cells/μl) showed a shorter overall survival. [432] Metastatic renal cell carcinoma Patients with a high blood neutrophil count (>6,000), intratumoral neutrophils and low intratumoral CD57 + NK cells are independent poor prognostic immunological factors.…”

Section: Prognostic Values Of Neutrophils and Other Myeloid Subtypes mentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

View full text Add to dashboard Cite

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.

show abstract

Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

Abstract: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

Cited by 385 publications

References 50 publications

Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

Subtypes of White Blood Cells in Patients with Prostate Cancer or Benign Prostatic Hyperplasia and Healthy Individuals

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Contact Info

Product

Resources

About