Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

Kuss, Iris; Donnenberg, Albert D.; Gooding, William E.; Tl, Whiteside

doi:10.1038/sj.bjc.6600694

Cited by 67 publications

(48 citation statements)

References 24 publications

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“…The timing of Annexin V positivity correlates with other models of senescent-like phenotypes (19). Increases in Annexin V have been documented in CD27 À or CD28 À peripheral blood T cells in patients with cancer and in the aging population (37,38). One group found that after successful resection of head and neck tumors, the number of CD3 + CD28 À cells decreased (7).…”

Section: Discussionmentioning

confidence: 93%

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

Montes¹,

Chapoval²,

Nelson³

et al. 2008

Cancer Research

118

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Senescent and suppressor T cells are reported to be increased in select patients with cancer and are poor prognostic indicators. Based on the association of these T cells and poor outcomes, we hypothesized that tumors induce senescence in T cells, which negatively effects antitumor immunity. In this report, we show that human T cells from healthy donors incubated with tumor for only 6 h at a low tumor to T-cell ratio undergo a senescence-like phenotype, characterized by the loss of CD27 and CD28 expression and telomere shortening. Tumor-induced senescence of T cells is induced by soluble factors and triggers increases in expression of senescence-associated molecules such as p53, p21, and p16. Importantly, these T cells are not only phenotypically altered, but also functionally altered as they can suppress the proliferation of responder T cells. This suppression requires cell-to-cell contact and is mediated by senescent CD4 + and CD8 + subpopulations, which are distinct from classically described natural T regulatory cells. Our observations support the novel concept that tumor can induce senescent T cells with suppressor function and may effect both the diagnosis and treatment of cancer. [Cancer Res 2008;68(3):870-9]

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Section: Discussionmentioning

confidence: 93%

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

Montes¹,

Chapoval²,

Nelson³

et al. 2008

Cancer Research

118

View full text Add to dashboard Cite

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“…Removal of HPVϩ tumors then removes this antigen source, whereas DCs may present antigen for prolonged periods of time, perhaps continuing to prime CTL (36). Also, because DC are known to prime the most active and long-lived T cells phenotypically, potentially preventing terminal differentiation leading to premature apoptosis in cancer patients (37), this is one potential explanation for differential fate of T cells generated after the removal of HPVϩ versus HPVϪ tumors. We are currently pursuing this issue mechanistically, in future experiments analyzing PBMCs from such squamous cell carcinoma of the head and neck patient populations.…”

Section: Discussionmentioning

confidence: 99%

Effect of Human Papillomavirus-16 Infection on CD8+ T-Cell Recognition of a Wild-Type Sequence p53264–272 Peptide in Patients with Squamous Cell Carcinoma of the Head and Neck

Sirianni

Ha²,

Oelke

et al. 2004

Clinical Cancer Research

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Purpose: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, currently considered primarily for patients whose tumors overexpress p53. Circumstances exist, however, where increased p53 degradation may result in appreciable presentation of p53-derived peptides, despite low p53 expression. Squamous cell carcinoma of the head and neck is associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate p53 through proteasomal degradation. The criterion of p53 overexpression would exclude these individuals from wt p53-based immunotherapy.Experimental

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“…44 Interestingly, in such patients, the accelerated turnover of differentiated T cells, compared with naive T lymphocytes, has been correlated to the increased susceptibility to apoptosis of cells at the effector stage. 45 On the other hand, we did not find evidence for increased annexin V binding in CCR7 Ϫ T cells from patients of this study, compared with CCR7 ϩ cells, as it may be expected to support an increased rate of elimination, by apoptosis, of differentiated T cells.…”

Section: Discussionmentioning

confidence: 40%

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with γc cytokines

Anichini

Mortarini

Romagnoli

et al. 2006

Blood

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The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4 ؉ and CD8 ؉ T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells show- IntroductionIndolent non-Hodgkin lymphomas (NHLs) arise from transformation of relatively well-differentiated, antigen-responsive Blymphocytes present in germinal centers. 1 Although neoplastic transformation at early stages of B-cell development usually results in aggressive diseases, malignant clonal proliferation of mature B cells generally leads to indolent B-cell lymphomas, 1 although clinical courses can show a considerable heterogeneity even within the same histologic subtype. This reflects the emerging complexity in the biologic and molecular basis of these diseases. 2,3 Although the available therapeutic strategies for indolent B-cell lymphoma, such as standard chemotherapy, high-dose chemotherapy, and bone marrow transplantation, have improved the outcome of these diseases, the majority of patients are not cured. 1 For these reasons, other approaches, including immunotherapy, 4 are being currently investigated, based on the evidence indicating that these tumors may be responsive to T-cell-mediated immunity in vivo. This has been suggested by the evidence for a prognostic significance of CD4 ϩ T cells at tumor site 5,6 and, more recently, by the identification of a molecular signature of tumor-infiltrating lymphocytes that predicts improved survival in patients with follicular lymphoma (FL). 7 Moreover, several B-cell NHLs (BNHLs) have been shown to express an array of T-cell-defined epitopes, such as those encoded by the tumor-specific B-cell receptor, 8,9 by CD19 and CD20 differentiation antigens, 10 or by overexpressed genes as BCL2 11 and fibromodulin. 12 These determinants represent attractive candidates for vaccination approaches, and initial results of studies targeting the B-cell idiotype have documented clinical responses in some patients. 4 In addition, these studies have shown that it is possible to boost/promote T-cellmediated responses to autologous B-cell tumor in the majority of vaccinated patients. 12 These findings point to the existence of a significant pool of tumor-specific T cells even in untreated patients. However, the often unfavorable clinical evolution of these diseases suggests that activation of effective antitumor immunity may be frequently impaired in vivo. To investigate this possibility we evaluated phenotype, function, antitumor activity, and maturation profile of CD4 ϩ and CD8 ϩ T cells from a large panel of patients with B-NHL. The results indicated that T cells from tumor site of these patients frequently show an activated phenotype but a low frequency of tumor-reactive effe...

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Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

Cited by 67 publications

References 24 publications

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

Effect of Human Papillomavirus-16 Infection on CD8+ T-Cell Recognition of a Wild-Type Sequence p53264–272 Peptide in Patients with Squamous Cell Carcinoma of the Head and Neck

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with γc cytokines

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