Localization of FOXP3-positive cells in renal cell carcinoma

Sell, Katharina; Barth, Peter; Moll, Roland; Thomas, Martin A.; Zimmer, Nadine; Oplesch, Ecatarina; Gudo, Michael; Schrader, Mark; Hofmann, Rainer; Schrader, Andres Jan

doi:10.1007/s13277-011-0283-1

Cited by 15 publications

(12 citation statements)

References 23 publications

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“… 15 Opposing the antitumor activity of CD8 T cells is a population of CD4 + T cells that express the forkhead box P3 (FOXP3) transcription factor, and which have a regulatory activity on the host immune response (known as Tregs). 16 Tregs play a crucial role in maintaining immune homeostasis and mediating peripheral tolerance, accordingly it has been shown that mice lacking FoxP3 develop an autoimmune phenotype. 17 Infiltration by regulatory T cells has been reported in a variety of malignancies including MIBC, lung cancer, breast cancer, and others in which their presence tends to portend a poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder

Baras¹,

Drake²,

Liu³

et al. 2016

OncoImmunology

147

113

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Introduction: Randomized controlled trials of platinum-based neoadjuvant chemotherapy (NAC) for bladder cancer have shown that patients who achieve a pathologic response to NAC exhibit 5 y survival rates of approximately 80–90% while NAC resistant (NR) cases exhibit 5 y survival rates of approximately 30–40%. These findings highlight the need to predict who will benefit from conventional NAC and the need for plausible alternatives. Methods: The pre-treatment biopsy tissues from a cohort of 41 patients with muscle invasive bladder who were treated with NAC were incorporated in tissue microarray and immunohistochemistry for PD-L1, CD8, and FOXP3 was performed. Percentage of PD-L1 positive tumor cells was measured. Tumor-infiltrating lymphocytes (TIL) densities, along with CD8 and Treg-specific TILs, were measured. Results: TIL density was strongly correlated with tumor PD-L1 expression, consistent with the mechanism of adaptive immune resistance in bladder cancer. Tumor cell PD-L1 expression was not a significant predictor of response. Neither was the CD8 nor Treg TIL density associated with response. Intriguingly though, the ratio of CD8 to Treg TIL densities was strongly associated with response (p = 0.0003), supporting the hypothesis that the immune system plays a role in the response of bladder cancer to chemotherapy. Discussion: To our knowledge, this is the first report in bladder cancer showing that the CD8 to Treg TIL density in the pre-treatment tissues is predictive for conventional NAC response. These findings warrant further investigations to both better characterize this association in larger cohorts and begin to elucidate the underlying mechanism(s) of this phenomenon.

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Section: Introductionmentioning

confidence: 99%

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder

Baras¹,

Drake²,

Liu³

et al. 2016

OncoImmunology

147

113

View full text Add to dashboard Cite

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“…There is currently no evidence of a direct link between HIES and RCC, but immunological factors relevant to each condition may account for a possible association that has not yet been recognized. Recent studies have demonstrated an increase in infiltrating Th17 and FoxP3 cells within the tumor milieu of renal cell carcinoma [13, 14]. …”

Section: Discussionmentioning

confidence: 99%

Hyper IgE Syndrome and Renal Cell Carcinoma

Patel

Ferretti

Phillips

2017

Case Reports in Urology

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Hyper IgE Syndrome (HIES) is an immunodeficiency disorder characterized by increased serum levels of IgE, eczema, and recurrent cutaneous and pulmonary infections. In this report, we present, to our knowledge, the first documented case of renal cell carcinoma (RCC) found in a patient with HIES. The patient received infectious disease clearance prior to obtaining a partial nephrectomy which revealed clear cell histology. Both HIES and RCC have an immunological basis for their pathophysiology and may involve common pathways. Further studies may provide insight into any possible link and clinicians should be mindful of immunocompromised patients who present with risk factors for genitourinary malignancy.

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“…Higher numbers of Foxp3+ Tregs in the peripheral blood or tumor bed were predictive of shortened overall survival as well as shortened disease-free survival (79,81,83,85). Additionally, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression, as well as between Tregs frequency and microvessel density score (80), suggesting that the level of Treg infiltrate correlated with angiogenic status.…”

Section: B Pathological Generation Of Inhibitory Immune Cells As a Cmentioning

confidence: 99%

Modification of the Tumor Microenvironment as a Novel Target of Renal Cell Carcinoma Therapeutics

Finke

Rayman

et al. 2013

The Cancer Journal

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To move forward with immunotherapy it is important to understand how the tumor microenvironment generates systemic immunosuppression in patients with renal cell carcinoma (RCC) as well as in patients with other types of solid tumors. Even though antigen discovery in RCC has lagged behind melanoma, recent clinical trials have finally authenticated that RCC is susceptible to vaccine-based therapy. Furthermore, judicious coadministration of cytokines and chemotherapy can potentiate therapeutic responses to vaccine in RCC and prolong survival, as has already proved possible for melanoma. While high dose interleukin-2 immunotherapy has been superseded as first line therapy for RCC by promiscuous receptor tyrosine kinase inhibitors (rTKI) such as sunitinib, sunitinib itself is a potent immunoadjunct in animal tumor models. A reasonable therapeutic goal is to unite anti-angiogenic strategies with immunotherapy as first line therapy for RCC. This strategy is equally appropriate for testing in all solid tumors in which the microenvironment generates immunosuppression. A common element of RCC, pancreatic, colon, breast and other solid tumors is large numbers of circulating myeloid-derived suppressor cells (MDSC), and because MDSC elicit regulatory T cells rather than vice versa, gaining control over MDSC is an important initial step in any immunotherapy. While rTKI like sunitinib have a remarkable capacity to deplete MDSC and restore normal T cell function in peripheral body compartments such as the bloodstream and the spleen, such rTKI are only effective against MDSC which are engaged in phosphoSTAT3-dependent programming (pSTAT3+). Unfortunately, rTKI-resistant pSTAT3- MDSC are especially apt to arise within the tumor microenvironment itself, necessitating strategies which do not rely exclusively upon STAT3 disruption. The most utilitarian strategy to gain control of both pSTAT3+ and pSTAT3- MDSC may be to exploit the natural differentiation pathway which permits MDSC to mature into tumoricidal macrophages (TM1) via such stimuli as TLR agonists, IFN-γ and CD40 ligation. Overall, this review highlights the mechanisms of immune suppression employed by the different regulatory cell types operative in RCC as well as other tumors. It also describes the different therapeutic strategies to overcome the suppressive nature of the tumor microenvironment.

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Localization of FOXP3-positive cells in renal cell carcinoma

Cited by 15 publications

References 23 publications

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder

Hyper IgE Syndrome and Renal Cell Carcinoma

Modification of the Tumor Microenvironment as a Novel Target of Renal Cell Carcinoma Therapeutics

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