IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo

Benatar, Tania; Cao, Ming; Lee, Yoon; Lightfoot, Jeff; Feng, Ningping; Gu, Xiaoping; Lee, Vivian; Jin, Hongnan; Wang, Ming; Wright, Jim A.; Young, Aiping

doi:10.1007/s00262-009-0802-8

Cited by 88 publications

(81 citation statements)

References 47 publications

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“…Understanding the molecular mechanisms involved in the cross-talk between eosinophils and CRC cells would certainly contribute to improve the existing knowledge of the immunogenic characteristics of the disease and may have a major impact in the development of novel therapeutic targets. 6,9,11,26,28,29,[31][32][33][34][35] In the case of CRC, eosinophil recruitment, activation and survival was suggested to be dependent on local production of IL-5 by tissue resident eosinophils 36 and active damage associated molecular pattern (DAMP) molecules, namely high mobility group box 1 (HMGB1), in the context of tumour cell necrosis. 32 Surprising findings have been achieved on the role of eotaxins in eosinophil chemoatraction to CRCs, since low numbers of tissue eosinophils are found both in primary CRCs 10,37 and liver metastases, 37 albeit not always associated with low levels of tissue eotaxins.…”

Section: Discussionmentioning

confidence: 99%

“…35 Thus, eosinophils may be engaged in the anti-tumour effect of IL-17E, and IL-17E was endorsed as a putative effective therapy in colon adenocarcinoma. 35 In addition to the aforementioned molecular mechanisms, the relation between eosinophils and other immune cells raises the hypotheses that eosinophils may also exert their action via other cells and vice-versa. 9,15,19 The interaction between eosinophils and other immune cells has been recognized.…”

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New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

Saraiva

Carneiro²

2018

Acta Med Port

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RESUMOIntrodução: O papel dos eosinófilos na carcinogénese colorretal tem sido discutido em várias publicações científicas. O objetivo deste estudo foi o de rever o valor dos eosinófilos tecidulares no prognóstico do cancro colorretal, enfatizando a sua identificação, mensuração e associação com as características clinicopatológicas da doença. Material e Métodos:Utilizámos os motores de busca PubMed e Web of Science para pesquisar estudos que associassem os eosinófilos tecidulares com o prognóstico do cancro colorretal.Resultados: Selecionámos 15 estudos para a nossa revisão. Maioritariamente, a análise do infiltrado foi realizada através da coloração de hematoxilina-eosina, com criação de scores. A maioria dos trabalhos descreveu a eosinofilia tecidular como um fator de prognóstico favorável no cancro colorretal e estabeleceu uma associação inversa entre ela e o comportamento metastático dos tumores. A associação com outros fatores de prognóstico foi por vezes abordada, com resultados inconsistentes. A eosinofilia tecidular diminuiu na progressão adenoma-carcinoma. Discussão:Vários mecanismos têm sido propostos para explicar a quimiotaxia de eosinófilos para os tecidos tumorais e a sua interação com as células neoplásicas, sugerindo o envolvimento dos eosinófilos na progressão do cancro colorretal. Apesar de não existir um sistema de avaliação validado, a eosinofilia tecidular associada a tumores pode constituir um parâmetro histopatológico de prognóstico no cancro colorretal. Conclusão:As evidências disponíveis associam a presença de eosinófilos no microambiente do cancro colorretal com a modulação da sua progressão. O impacto clínico deste achado deve ser estudado no futuro. Palavras-chave: Material and Methods:We used PubMed and Web of Science search engines to retrieve studies that looked at the association between tissue eosinophils and colorectal cancer prognosis. Results:We selected 15 studies for our review. In the majority of the studies, eosinophils were identified in hematoxylin-eosin stained sections and scores were generated for analysis. Most of the studies pointed to tumour-associated tissue eosinophilia as a favourable prognostic marker in colorectal cancer and found an inverse association between eosinophil count and the metastatic potential of these neoplasms. The association between tumour-associated tissue eosinophilia and established prognostic markers of colorectal cancer was assessed in some studies, with inconsistent results. Additionally, tumour-associated tissue eosinophilia decreased with the adenoma-carcinoma progression of colorectal lesions.Discussion: Several mechanisms have been proposed regarding eosinophil chemoatraction to tumour tissues and eosinophil-cancer cell cross-talk, suggesting that eosinophils are actively involved in colorectal cancer progression. Although a scoring system is still lacking, tumour-associated tissue eosinophilia meets the criteria of a convenient histopathological prognosticator in colorectal cancer. Conclusion:Collectively, current evidence associa...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

Saraiva

Carneiro²

2018

Acta Med Port

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“…Interestingly, B cells comprised 57% of infiltrating cells in benign glands; this number was significantly reduced in malignant glands. Inflammatory cytokines including TNFα, IL-6, and IL-8 play an important role in oncogenesis and tumor progression, whereas other kinds of cytokines including IL-17E have antitumour activity [26,27,28,29]. Thus, B cells contribute to both tumor progression and suppression.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Analysis of Inflammatory Cells in Benign and Precancerous Lesions and Carcinoma of the Prostate

Fujii¹,

Shimada²,

Asai

et al. 2013

Pathobiology

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Objective: Inflammation is an important cause of tumorigenesis in various types of malignancy. Mediators derived from inflammatory cells are associated with cancer proliferation, angiogenesis, and DNA damage. In the present study, we immunohistochemically examined the infiltration patterns of inflammatory cells in benign glands including glandular hyperplasia, and in prostatic intraepithelial neoplasia and adenocarcinoma. Methods: Formalin-fixed, paraffin-embedded tissues were obtained from 100 patients with prostate cancer. All patients underwent radical prostatectomy. We assessed the number of infiltrating T cells (CD3⁺), B cells (CD20⁺, CD79alpha⁺), and macrophages (CD68⁺, CD204⁺) in benign and malignant prostate tumors. Results: CD68⁺ macrophages infiltrated benign glands to a higher extent than those of adenocarcinoma. In contrast, the number of CD204⁺ cells was higher in malignant glands than in benign glands. There was no significant difference in the number of infiltrating T cells between benign and malignant tumors; however, the number of infiltrating B cells was significantly reduced in malignant glands. Conclusions: Inflammation of the prostate may act on prostate carcinomas; particularly that involving M2 macrophage infiltration may play a significant role in prostate carcinogenesis.

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“…33 More recently, it has been demonstrated that IL-25 (synonym IL-17E), which is also released by eosinophils, exhibits antitumoral activity and leads to eosinphilia in a colorectal cancer xenograft model. 34 IL-25 may induce the expansion of eosinophils through IL-5 as well as elevated levels of IL-4 and IL-13, but also directly induce apoptosis of cancer cells. 35 Our study has strengths and limitations.…”

Section: Discussionmentioning

confidence: 99%

Peritumoral eosinophils predict recurrence in colorectal cancer

et al. 2015

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In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri-and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri-and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R ¼ 0.69; Po0.001) and with the intensity of the overall inflammatory cell reaction (R ¼ 0.318; Po0.001). Both increasing peri-and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P ¼ 0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P ¼ 0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/ UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising readily assessable tool and should therefore routinely be commented on in the pathology report.

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IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo

Cited by 88 publications

References 47 publications

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

Immunohistochemical Analysis of Inflammatory Cells in Benign and Precancerous Lesions and Carcinoma of the Prostate

Peritumoral eosinophils predict recurrence in colorectal cancer

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