Evaluation of tumour-infiltrating CD4+CD25+FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases

Mourmouras, Vasileios; Fimiani, Michele; Rubegni, Pietro; Epistolato, Maria Carmela; Malagnino, Valeria; Cardone, Concetta; Cosci, Elena; Nisi, Maria Caterina De; Miracco, Clelia

doi:10.1111/j.1365-2133.2007.08057.x

Cited by 54 publications

(45 citation statements)

References 52 publications

(106 reference statements)

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“…We did not make attempts to characterize the labeled cell type(s) more precisely by double immunohistochemical staining. Although the expression of FOXP3 could be induced in vitro in CD4 + CD25 − and CD8 + lymphocytes as well [26][27][28][29], in previous immunohistochemical studies on melanoma all FOXP3 + cells expressed CD3 and almost all of them CD4 and CD25 as well [18,19], suggesting that the vast majority of tumor-infiltrating FOXP3 + cells are CD4 + CD25 + T lymphocytes.…”

Section: Discussionmentioning

confidence: 88%

“…Mourmouras et al characterized cutaneous melanocytic lesions including melanomas with respect to the prevalence of Tregs, and found a lower percentage of Tregs in vertical than in radial growth phase melanomas [18]. Contrary to this finding, another small-scale study described higher prevalence of these cells in VGP compared to RGP, and also in stage III-IV tumors compared to stage I ones [19].…”

Section: Introductionmentioning

confidence: 95%

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FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Ladányi

Mohos

Somlai

et al. 2010

Pathol. Oncol. Res.

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Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4 + CD25 + Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3 + cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3 + cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3 + lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 95%

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Ladányi

Mohos

Somlai

et al. 2010

Pathol. Oncol. Res.

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“…+ cells have been considered to represent Tregs in previous reports [20,21], we analysed the prevalence of CD25…”

Section: Foxp3mentioning

confidence: 99%

Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients

Yip

Abdullah

Yusoff

et al. 2009

Clinical and Experimental Immunology

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SummaryThe pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a doubleenzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 nonmalignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3z and CD3e was also determined. The prevalence of CD4 + FoxP3 + cells in CD4 + T cells and the ratio of FoxP3 + /CD8 + were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3 NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25 + FoxP3 -cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3 + /CD25 + FoxP3 -was found in non-keratinizing and undifferentiated carcinomas. Increased CD4 + FoxP3 + /CD4 + proportion and FoxP3 + /CD8 + ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3z in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.

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“…However, clinical studies (11,13) (17,18). Certain studies have identified increased peripheral Treg levels in patients with metastatic MM (19)(20)(21)(22)(23); therefore, therapies that decrease Treg levels may be beneficial for these patients.…”

Section: Introductionmentioning

confidence: 99%

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study

Chen

Zhao

et al. 2016

Oncology Letters

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Abstract. The present study aimed to evaluate the efficacy and safety of in situ immunotherapy with dinitrophenyl (DNP) hapten in combination with laser therapy for patients with malignant melanoma (MM). Between February 2008 and March 2012, 72 patients with stage III or IV MM were enrolled. Patients received in situ DNP alone (n=32) or in combination with laser therapy (n=32), and each group received dacarbazine chemotherapy. The levels of peripheral cluster of differentiation (CD)4 + CD25 + regulatory T cells (Tregs), interleukin (IL)-10 and tumor growth factor (TGF)-β were detected by ELISA. The association between delayed-type hypersensitivity (DTH) and survival time was evaluated. Although peripheral Treg levels significantly decreased over time in the two groups (P<0.001), there was no significant difference between the treatment groups (P= 0.098). Patients receiving the combination treatment exhibited significantly higher interferon-γ production by CD8 + and CD4 + T cells (both P<0.001), as well as significantly reduced levels of IL-10, TGF-β1 and TGF-β2. In addition, patients in the combination treatment group experienced significantly longer overall survival (OS; P=0.024) and disease-free survival (DFS; P=0.007) times; a DTH response of ≥15 mm was also associated with increased OS time and DFS time (P≤0.001). Finally, no severe adverse events were observed in either treatment group. Overall, in situ immunization with DNP in combination with laser immunotherapy may activate focal T cells, producing a regional antitumor immune response that increases cell-mediated immunity and improves survival in MM patients. Thus, this may represent a novel therapeutic strategy for patients with unresectable, advanced MM. IntroductionDerived from neural crest cells, malignant melanoma (MM) accounts for ~1.5% of all tumors and is the cutaneous malignancy with the highest mortality rate (1). There are >10 million new cases of MM diagnosed every year (1). In total, ~21% of MM patients present with focal skin metastasis and 50% with regional lymph node metastasis (1). MM patients with distant metastasis (stage IV) usually have poor prognoses, with a median survival time of 5-8 months, and the ≥5-year survival rate is <2% (2). With social and economic development, the incidence of MM is increasing each year (3).The poor prognosis of MM patients is reflective of the lack of an effective therapy. Systemic chemotherapy, including mono-and poly-chemotherapies, immunomodulatory therapies and vaccination therapy with dendritic cells (DCs) or genetically modified tumor cells, remains controversial (2). Although there is evidence showing that the combined use of interleukin (IL)-2, interferon (IFN) and chemotherapeutics may achieve a response rate as high as 64% (4,5), the efficacy of systemic therapy remains disappointing; systemic monotherapy usually achieves a clinical response rate of <15% (6-10). However, prospective, randomized clinical trials have shown no evidence that other drugs are superior to dacarbazine (DTIC) for MM pa...

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Evaluation of tumour-infiltrating CD4+CD25+FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases

Cited by 54 publications

References 52 publications

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study

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