The intriguing role of polymorphonuclear neutrophils in antitumor reactions

Carlo, Emma Di; Forni, Guido; Lollini, Pier‐Luigi; Colombo, Mario P.; Modesti, Andrea; Musiani, Piero

doi:10.1182/blood.v97.2.339

Cited by 371 publications

(310 citation statements)

References 86 publications

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“…The significance of polymorphonuclear neutrophil infiltration in tumors is a matter of controversy, as in mice polymorphonuclear neutrophils effectively inhibit tumor growth. 43 In humans, high polymorphonuclear neutrophil infiltration in the tumor was associated with a poorer outcome possibly due to the release of proteases, angiogenic factors or growth factors. 44,45 The prognostic value of IL-17 expression by MF/SS tumors was not addressed in this study.…”

Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4 ؉ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3 ؉ CD4 ؉ CD45RO ؉ , a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.

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Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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“…36 -38 These different outcomes are probably the result of interplay between the cytokine/chemokine profile and the degree of activation of intratumor PMNs. 39 Alternatively, the presence of necrotic cells in the microenvironment as a consequence of impaired clearance of apoptotic cells may alter the balance between induction and inhi- bition of an inflammatory response defined by mononuclear phagocytes, 40 which in turn orchestrate neutrophil behavior.…”

Section: Discussionmentioning

confidence: 99%

Transient inflammatory response induced by apoptotic cells is an important mediator of melanoma cell engraftment and growth

Correa

Machado

Carneiro

et al. 2004

Intl Journal of Cancer

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The current model for cancer development outlines a multistep process during which a cell acquires multiple genetic mutations. 1 However, several lines of investigation suggest that concomitant changes also occur in the surrounding tissue, with important consequences in the induction, selection and expansion of neoplastic cells. 2-4 Specific host factors available both locally, such as the stroma and surrounding normal cells, and distally, via humoral or diffusible factors, can provide the necessary information to create a permissive environment for malignant cell growth. 5,6 In particular, ECM composition and growth factor activity in the stroma can enhance the tumorigenicity of subsequently injected tumor cell lines. 7 Additionally, many malignancies can be initiated by infection, 8 -10 suggesting that cancer may arise in areas of inflammation as part of the normal host response. For instance, solid human tumors are often infiltrated by host immune and inflammatory cells. 11 Whereas increased levels of leukocyte infiltration into primary tumors are usually a good prognostic sign, 12 the presence of inflammatory cell infiltrates has been correlated with cytokine and growth factor production, which may provide a favorable microenvironment for neoplastic proliferation. [13][14][15][16] Clearance of apoptotic cells by phagocytes plays a significant role in the resolution of inflammation, 17 and although the lack of an inflammatory infiltrate is by definition a hallmark of death by apoptosis, several lines of investigation have challenged this concept. Indeed, apoptotic cells can evoke an inflammatory response depending on how apoptosis is initiated, in what cell type it occurs and whether or not particular cofactors are present. 18 -21 Considering that the nature of the microenvironment is one of several factors involved in the failure of tumor cells to proliferate, we tested whether apoptotic cells present in the host tissue environment could promote the growth of tumor cells in vivo. Results showed that (i) the presence of apoptotic cells in the tumor microenvironment positively modulates tumor take when the number of tumor cells alone is insufficient to produce tumors, (ii) injection of apoptotic cells induces an inflammatory response with an intense recruitment of neutrophils and macrophages and (iii) inflammatory cells recruited by apoptotic cells may be an important factor in promoting tumor engraftment when suboptimal concentrations of tumor cells are used. Taken together, our results provide new insights for the mechanisms underlying the microenvironment helper effect, with potential clinical implications for cancer therapy. Material and methods Cell culture, proliferation assay and reagentsThe murine melanocyte cell line melan-a (50th passage), 22 a kind gift of Dr. M. Rabinovitch (Discipline of Parasitology, Universidade Federal de São Paulo), was cultured in RPMI (pH 6.9) supplemented with 5% FCS and 200 nM 12-o-tetradecanoyl PMA (Sigma, St. Louis, MO). Tumor cell lines derived from melan-a (Tm1 and...

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“…It is noteworthy to point out that molecules other than H 2 O 2 , HOCl and NO· may also mediate the tumoricidal effects of neutrophils. These include proteases [331], membraneperforating agents [331], TNFα [331,332], TRAIL [333] and defensins [334,335].…”

Section: Direct Cytotoxicitymentioning

confidence: 99%

“…Another mechanism for neutrophil-mediated tumor cell killing is antibody-dependent cell-mediated cytotoxicity (ADCC) [7,331] where specific antibodies are used to target malignant cells. Neutrophils express several subtypes of FcRs capable of inducing ADCC, including FcγRI (CD64), FcγRIIa (CD32), FcγRIIIa (CD16a), and FcγRIIIb (CD16b) [336][337][338], whose surface expression is increased following G-CSF stimulation [338,339].…”

Section: Antibody-dependent Cell-mediated Cytotoxicity (Adcc)mentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

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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The intriguing role of polymorphonuclear neutrophils in antitumor reactions

Cited by 371 publications

References 86 publications

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Transient inflammatory response induced by apoptotic cells is an important mediator of melanoma cell engraftment and growth

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

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