Tumor-host interaction: Analysis of cytokines, growth factors, and tumorinfiltrating lymphocytes in ovarian carcinomas

Merogi, Athir J.; Marrogi, Aizen J.; Ramesh, Rajagopal; Robinson, William R.; Fermin, César D.; Freeman, Scott

doi:10.1016/s0046-8177(97)90131-3

Cited by 101 publications

(73 citation statements)

References 44 publications

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“…Our results confirm that cancer cells may attain immune escape by changing the effector composition of the host immune cells. We further explore the issues of proposed cancer-host immune interactions based on previous in vivo murine models and in vitro cell line results (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

“…TGF-␤ and IL-10 are secreted spontaneously by a variety of human malignant tumors, including breast, colon, ovary, cutaneous basal/squamous cancers, metastatic melanoma, fibrosarcoma, and pancreatic carcinoma (27)(28)(29)(30)(31)(32)(33)(34)(35). The mechanisms responsible for the increased expression by tumor cells are not known.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms responsible for the increased expression by tumor cells are not known. It has been suggested that tumor-derived IL-10 may be associated with the down-regulation of anti-tumor immunity by inhibiting the cytotoxicity of CTLs, tumor Ag presentation, and Th1 cell development (27,28,35,36). However, related studies in the literature showed indirect evidences of either elevated IL-4 and IL-10 mRNA, or mixed type 2 cytokine patterns in cancers (28,37,38).…”

Section: Discussionmentioning

confidence: 99%

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Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Sheu

Lin

Lien

et al. 2001

The Journal of Immunology

182

115

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Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-γ in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-β plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-β Abs. IL-10 and TGF-β are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-β in cancer-mediated immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Sheu

Lin

Lien

et al. 2001

The Journal of Immunology

182

115

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“…Some studies suggest that patients with recurrent prostate, breast or ovarian cancer exhibit higher levels of IL-8 in serum or peripherical blood leukocytes (Merogi et al, 1997;Ivarsson et al, 1998;Veltri et al, 1999) and in cancer tissues (Green et al, 1997). On the contrary, other studies show that IL-8 expression in breast tumors is identical between normal and cancer tissues (Speirs et al, 1996).…”

Section: --------------------------------------------------------"mentioning

confidence: 99%

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

et al. 2003

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Estrogen-receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that interleukin-8 (IL-8) was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ERnegative MDA-MB-231 cells, and we show that IL-8 produced by breast cancer cells is identical to monocytederived IL-8. Interestingly, the invasion potential of ERnegative breast cancer cells is associated at least in part with expression of IL-8, but not with IL-8 receptor levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by two fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ERnegative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness.

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“…Ovarian tumours may contain a significant number of infiltrating host leukocytes, and in the case of ovarian cancers, these are predominantly macrophages and T cells (Merogi et al, 1997;Negus et al, 1997). The likely stimulus for the presence of these leukocytes is the local production of chemokines.…”

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confidence: 99%

Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma

et al. 2005

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Chemokine (C-C motif) ligand-2 (CCL2) is a chemoattractant and activator of macrophages and is a key determinant of the macrophage infiltrate into tumours. We demonstrate here that CCL2 is expressed in normal human ovarian surface epithelium (HOSE) cells and is silenced in most ovarian cancer cell lines, and silenced or downregulated in the majority of primary ovarian adenocarcinomas. Analysis of the CCL2 locus at 17q11.2 -q12 showed loss of heterozygosity (LOH) in 70% of primary tumours, and this was significantly more common in tumours of advanced stage or grade. However, we did not detect any mutations in the CCL2 coding sequence in 94 primary ovarian adenocarcinomas. These data support the hypothesis that CCL2 may play a role in the pathobiology of ovarian cancers, but additional studies will be required to evaluate this possibility.

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Tumor-host interaction: Analysis of cytokines, growth factors, and tumorinfiltrating lymphocytes in ovarian carcinomas

Cited by 101 publications

References 44 publications

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma

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