Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients

Dielmann, Anastasia; Letsch, Anne; Nonnenmacher, Anika; Miller, Kurt; Keilholz, Ulrich; Busse, Antonia

doi:10.1007/s00262-015-1786-1

Cited by 16 publications

(17 citation statements)

References 48 publications

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“…Balermpas P et al found no correlation between CD4 expression and clinical outcome of patients with head and neck cancer [15], whereas Nguyen N et al reported that higher CD4 levels predicted improved OS and disease-specific survival [17]. T-bet has been shown to be associated with better outcome in patients with renal cell cancer, breast cancer, gastric cancer and colorectal cancer [19, 42–45]. We did not observe any correlation for either CD4 or T-bet expression and clinical outcome in our series.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma

Fang¹,

Li²,

Ma³

et al. 2017

BMC Cancer

135

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BackgroundPrognostic factors aid in the stratification and treatment of cancer. This study evaluated prognostic importance of tumor infiltrating immune cell in patients with oral squamous cell carcinoma.MethodsProfiles of infiltrating immune cells and clinicopathological data were available for 78 OSCC patients with a median follow-up of 48 months. The infiltrating intensity of CD8, CD4, T-bet, CD68 and CD57 positive cells were assessed by immunohistochemistry. Chi-square test was used to compare immune markers expression and clinicopathological parameters. Univariate and multivariate COX proportional hazard models were used to assess the prognostic discriminator power of immune cells. The predictive potential of immune cells for survival of OSCC patients was determined using ROC and AUC.ResultsThe mean value of CD8, CD4, T-bet, CD68 and CD57 expression were 28.99, 62.06, 8.97, 21.25 and 15.75 cells per high-power field respectively. The patient cohort was separated into low and high expression groups by the mean value. Higher CD8 expression was associated with no regional lymph node metastasis (p = 0.033). Patients with more abundant stroma CD57+ cells showed no metastasis into regional lymph node (p = 0.005), and early clinical stage (p = 0.016). The univariate COX regression analyses showed that no lymph node involvement (p < 0.001), early clinical stage (TNM staging I/II vs III/IV, p = 0.007), higher CD8 and CD57 expression (p < 0.001) were all positively correlated with longer overall survival. Multivariate COX regression analysis showed that no lymph node involvement (p = 0.008), higher CD8 (p = 0.03) and CD57 (p < 0.001) expression could be independent prognostic indicators of better survival. None of CD4, T-bet or CD68 was associated with survival in ether univariate or multivariate analysis. ROC and AUC showed that the predictive accuracy of CD8 and CD57 were all superior compared with TNM staging. CD57 (AUC = 0.868; 95% CI, 0.785–0.950) and CD8 (AUC = 0.784; 95% CI, 0.680–0.889) both provided high predictive accuracy, of which, CD57 was the best predictor.ConclusionTumor stroma CD57 and CD8 expression was associated with lymphnode status and independently predicts survival of OSCC patients. Our results suggest an active immune microenvironment in OSCC that may be targetable by immune drugs.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma

Fang¹,

Li²,

Ma³

et al. 2017

BMC Cancer

135

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“…Numerous studies have dealt with the role of Eomes in the exhaustion of CD8(+) T lymphocytes during chronic infections or cancers (68–72). Our results in healthy donors (HDs) attesting a significant proliferative response to IL-15 (Figure S4 in Supplementary Material) do not lend support to an exhaustion phenotype of innate CD8(+) T cells in normal conditions.…”

Section: Is There a Role For Innate Cd8(+) T Lymphocytes In Cancer Immentioning

confidence: 99%

Phenotype of NK-Like CD8(+) T Cells with Innate Features in Humans and Their Relevance in Cancer Diseases

et al. 2017

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Unconventional T cells are defined by their capacity to respond to signals other than the well-known complex of peptides and major histocompatibility complex proteins. Among the burgeoning family of unconventional T cells, innate-like CD8(+) T cells in the mouse were discovered in the early 2000s. This subset of CD8(+) T cells bears a memory phenotype without having encountered a foreign antigen and can respond to innate-like IL-12 + IL-18 stimulation. Although the concept of innate memory CD8(+) T cells is now well established in mice, whether an equivalent memory NK-like T-cell population exists in humans remains under debate. We recently reported that CD8(+) T cells responding to innate-like IL-12 + IL-18 stimulation and co-expressing the transcription factor Eomesodermin (Eomes) and KIR/NKG2A membrane receptors with a memory/EMRA phenotype may represent a new, functionally distinct innate T cell subset in humans. In this review, after a summary on the known innate CD8(+) T-cell features in the mouse, we propose Eomes together with KIR/NKG2A and CD49d as a signature to standardize the identification of this innate CD8(+) T-cell subset in humans. Next, we discuss IL-4 and IL-15 involvement in the generation of innate CD8(+) T cells and particularly its possible dependency on the promyelocytic leukemia zinc-finger factor expressing iNKT cells, an innate T cell subset well documented for its susceptibility to tumor immune subversion. After that, focusing on cancer diseases, we provide new insights into the potential role of these innate CD8(+) T cells in a physiopathological context in humans. Based on empirical data obtained in cases of chronic myeloid leukemia, a myeloproliferative syndrome controlled by the immune system, and in solid tumors, we observe both the possible contribution of innate CD8(+) T cells to cancer disease control and their susceptibility to tumor immune subversion. Finally, we note that during tumor progression, innate CD8(+) T lymphocytes could be controlled by immune checkpoints. This study significantly contributes to understanding of the role of NK-like CD8(+) T cells and raises the question of the possible involvement of an iNKT/innate CD8(+) T cell axis in cancer.

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“…Using animal models, the contribution of T-bet in anti-cancer immune responses, has been specifically attributed to its regulation of adaptive immune components like Th1 cells [13]. Numerous retrospective studies have also established that T-bet expression in human cancer tissues significantly associate with cancer progression and patients' prognoses [14][15][16][17]. In this regard, we have also previously reported that the higher numbers of infiltrating T-bet + lymphocytes in human gastric and esophageal cancer tissues were significantly associated with the patients' postoperative prognoses [9,10].…”

Section: Introductionmentioning

confidence: 99%

Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet⁺ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. Methods: The immunohistochemistry was used to analyze the infiltration density of T-bet⁺ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet⁺ tumor-infiltrating lymphocytes subgroups in cancer tissues. Results: Our immunohistochemistry analysis showed increased number of T-bet⁺ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet⁺ tumor-infiltrating lymphocytes subgroups including CD4⁺ , CD8⁺ T cells and NK cells. In addition, we also observed a significant association of T-bet⁺ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet⁺ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet⁺ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients’ postoperative prognoses. Conclusions: Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet⁺ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients.

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Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients

Cited by 16 publications

References 48 publications

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma

Phenotype of NK-Like CD8(+) T Cells with Innate Features in Humans and Their Relevance in Cancer Diseases

Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer

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