IFN-γ-Inducible Chemokines Enhance Adaptive Immunity and Colitis

Singh, Udai P.; Singh, Shailesh; Iqbal, Nuzhat; Weaver, Casey T.; McGhee, Jerry R.; Lillard, James W.

doi:10.1089/107999003322485099

Cited by 59 publications

(66 citation statements)

References 64 publications

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“…Both of these glutamate-leucine-arginine-negative CXC chemokines have the capacity to attract and retain activated T cells (58,59), and they both have been shown to have significant angiostatic activity that contributes to the inhibition of human NSCLC tumorigenesis and spontaneous metastases (60,61). Collectively, these findings illustrate the importance and potential capacity of fibroblasts in the tumor microenvironment to attract, retain, and modulate the activation of tumor-associated lymphocytes and to directly and indirectly alter the local progression and metastasis of human tumors.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Nazareth

Broderick

Simpson-Abelson

et al. 2007

The Journal of Immunology

229

191

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The tumor microenvironment of human non-small cell lung cancer (NSCLC) is composed largely of stromal cells, including fibroblasts, yet these cells have been the focus of few studies. In this study, we established stromal cell cultures from primary NSCLC through isolation of adherent cells. Characterization of these cells by flow cytometry demonstrated a population which expressed a human fibroblast-specific 112-kDa surface molecule, Thy1, α-smooth muscle actin, and fibroblast activation protein, but failed to express CD45 and CD11b, a phenotype consistent with that of an activated myofibroblast. A subset of the tumor-associated fibroblasts (TAF) was found to express B7H1 (PD-L1) and B7DC (PD-L2) constitutively, and this expression was up-regulated by IFN-γ. Production of cytokines and chemokines, including IFN-γ, monokine induced by IFN-γ, IFN-γ-inducible protein-10, RANTES, and TGF-β1 was also demonstrated in these cells. Together, these characteristics provide multiple opportunities for the TAF to influence cellular interactions within the tumor microenvironment. To evaluate the ability of TAF to modulate tumor-associated T cell (TAT) activation, we conducted coculture experiments between autologous TAF and TAT. In five of eight tumors, TAF elicited a contact-dependent enhancement of TAT activation, even in the presence of a TGF-β1-mediated suppressive effect. In the three other tumors, TAF had a net suppressive effect upon TAT activation, and, in one of these cases, blockade of B7H1 or B7DC was able to completely abrogate the TAF-mediated suppression. We conclude that TAF in human NSCLC are functionally and phenotypically heterogeneous and provide multiple complex regulatory signals that have the potential to enhance or suppress TAT function in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Nazareth

Broderick

Simpson-Abelson

et al. 2007

The Journal of Immunology

229

191

View full text Add to dashboard Cite

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“…This indicates that its expression can be specifically induced as the disease progresses. Previous studies have shown that CRC cells can produce CXCL10 (31) and that CXCL10 functions as a major chemoattractant for activated T cells and natural killer cells (33,34). Various studies have strongly suggested a role for CXCL10 in the regulation of angiogenesis activity in tumorigenesis (34), as well as in direct metastasis-promoting activities in CRC cells, and its influence in the tumor microenvironment (35).…”

Section: Discussionmentioning

confidence: 99%

Identification of an intermediate signature that marks the initial phases of the colorectal adenoma-carcinoma transition

Tang

Guo²,

Chao³

et al. 2010

Int J Mol Med

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Abstract. The colorectal adenoma-carcinoma sequence describes the stepwise progression from normal to dysplastic epithelium and then to carcinoma. Only a small proportion of colorectal adenomas (CRAs) progress to colorectal carcinomas (CRCs). Endoscopic intervention is currently being used on patients with high grade dysplasia CRAs, with diameters of >1 cm, or villous components of >25% who are at higher risk than other CRA sufferers. During the process, biopsy samples are taken for conventional histological diagnosis, but poor pathomorphological sensitivity and specificity greatly limit the diagnostic accuracy. Unfortunately, there are no reliable molecular criteria available that can predict the potential development of CRA to CRC. Gene expression profiles of normal colorectal mucosa (NOR), CRA and different Dukes' stages of CRC biopsy specimens, which represent the gradual progress of the CRA to CRC sequence, were determined by Affymetrix technology. Representative regulated genes were further analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Intersectional analyses of discriminative expression signatures of CRC vs. CRA and CRA vs. NOR allowed the identification of an intermediate signature of 463 probe sets (psets) that mark the NOR➝ CRA➝CRC progression. This signature represents a reservoir of candidate markers for the early diagnosis of higher-risk CRA, thus allowing for timely therapeutic intervention and more selective treatment. A further 279 CRC-specific psets pointing to the malignant transition from CRA to CRC were identified and these could represent potential therapeutic targets for CRC. The reliability of the results was further confirmed by qRT-PCR and IHC analyses of the 4-gene sets randomly selected from the 463 psets.

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“…CXC chemokines are important for enhancing immunity, regulating angiogenesis, and mediating tumor cell metastases (7). CXCL10, human interferon-inducible protein 10 (IP-10), acts through putative receptor CXC receptor 3 (CXCR3), and functions as a major chemoattractant for activated T cells and natural killer cells (8)(9)(10). Recently, numerous studies into the role of CXCL10 in malignancy have shown two tumor inhibiting properties that influence cells in the tumor microenvironment (11).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, numerous studies into the role of CXCL10 in malignancy have shown two tumor inhibiting properties that influence cells in the tumor microenvironment (11). One property is the recruitment into tumor sites of CXCR3-expressing mononuclear cells with antitumor activity and the other is antagonizing the effects of powerful angiogenic factors (8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer

Toiyama

Fujikawa²,

Kawamura³

et al. 2011

Int J Oncol

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Abstract. The aim of this study was to identify novel and reliable serum markers related to the prognosis of colorectal cancer (CRC) patients and to assess the association between selected markers and clinical outcome. We performed experiments using cytokine arrays to investigate the cytokine profiles in serum from stage IV CRC patients, compared with those of stage I patients. Serum CXCL10 was measured using an ELISA in 218 CRC patients and 17 normal volunteers to clarify the association of CXCL10 with clinical outcome. The mean serum CXCL10 concentration in CRC patients was significantly higher compared to that in normal volunteers. Serum CXCL10 levels increased significantly in accordance with the progression of UICC stage classification. Serum CXCL10 was significantly associated with high pathological T stage, the presence of vascular invasion and distant metastasis. Elevated serum CXCL10 levels were significantly associated with poor survival in all stages or in stage I-III with curative patients, respectively, and were an independent marker in predicting liver metastasis. Immunohistochemical analysis showed that CXCL10 was expressed in cancer cells at primary tumor and liver metastases sites, and in normal liver tissue surrounding metastatic cancer cells. Comprehensive analysis using cytokine arrays identified the novel serum prognosis marker CXCL10. Preoperative high serum levels of CXCL10 were associated with poor prognosis and liver metastasis in CRC.

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IFN-γ-Inducible Chemokines Enhance Adaptive Immunity and Colitis

Cited by 59 publications

References 64 publications

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Identification of an intermediate signature that marks the initial phases of the colorectal adenoma-carcinoma transition

Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer

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