Expression of Pro- and Antiapoptotic Proteins in Circulating CD8+ T Cells of Patients with Squamous Cell Carcinoma of the Head and Neck

Kim, Jeong‐Whun; Tsukishiro, Takashi; Johnson, Jonas T.; Whiteside, Theresa L.

doi:10.1158/1078-0432.ccr-04-0309

Cited by 43 publications

(37 citation statements)

References 22 publications

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“…The population of iMCs is a heterogeneous mixture of precursors of different myeloid cells and early progenitors, therefore, whether the inhibitory effect of iMCs is limited to CD8+ T cells or is extended to CD4+ T cells may depend on the expression of MHC antigens on the iMC surface. In fact, the increased sensitivity of CD8+ T cells to apoptosis-which is due to the elevated Bax/Bcl-2 ratio on the T cells, Fas/Fas-ligand interactions, and high levels of FasL expression on the tumorhave been observed in patients with head and neck cancer (52), breast cancer (53), and oral cancer (54). Furthermore, microvesicleassociated FasL-induced decreased expression of TCR-~, which is a substrate of caspase-3, leads to altered signal transduction in T cells and apoptosis (55).…”

Section: Role Of Vegf and Imcs In Immune Evasionmentioning

confidence: 99%

Tumor-Driven Evolution of Immunosuppressive Networks during Malignant Progression

Kim¹,

et al. 2006

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Tumors evolve mechanisms to escape immune control by a process called immune editing, which provides a selective pressure in the tumor microenvironment that could lead to malignant progression. A variety of tumor-derived factors contribute to the emergence of complex local and regional immunosuppressive networks, including vascular endothelial growth factor, interleukin-10, transforming growth factor-B, prostaglandin E 2 , and soluble phosphatidylserine, soluble Fas, soluble Fas ligand, and soluble MHC class I-related chain A proteins. Although deposited at the primary tumor site, these secreted factors could extend immunosuppressive effects into the local lymph nodes and the spleen, promoting invasion and metastasis. Vascular endothelial growth factors play a key role in recruiting immature myeloid cells from the bone marrow to enrich the microenvironment as tumor-associated immature dendritic cells and tumor-associated macrophages. The understanding of the immunosuppressive networks that evolve is incomplete, but several features are emerging. Accumulation of tumor-associated immature dendritic cells may cause roving dendritic cells and T cells to become suppressed by the activation of indoleamine 2,3-dioxygenase and arginase I by tumor-derived growth factors. Soluble phosphatidylserines support tumor-associated macrophages by stimulating the release of anti-inflammatory mediators that block antitumor immune responses. Soluble Fas, soluble FasL, and soluble MHC class I-related chain A proteins may help tumor cells escape cytolysis by cytotoxic T cells and natural killer cells, possibly by counterattacking immune cells and causing their death. In summary, tumor-derived factors drive the evolution of an immunosuppressive network which ultimately extends immune evasion from the primary tumor site to peripheral sites in patients with cancer. (Cancer Res 2006; 66(11): 5527-36)

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Section: Role Of Vegf and Imcs In Immune Evasionmentioning

confidence: 99%

Tumor-Driven Evolution of Immunosuppressive Networks during Malignant Progression

Kim¹,

et al. 2006

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“…74 By using T-cell receptor excision circle (TREC) analysis, a PCRbased technique that allows for quantification of recent thymic emigrants in the peripheral circulation, it has been determined that patients with cancer had significantly fewer recent thymic emigrants than healthy age-matched donors. 67 The results suggest that the lymphocyte turnover is faster in patients with cancer than in healthy control subjects, either because the thymic output in patients is lower or the peripheral expansion of T cells is greater, diluting T-cell receptor excision circles and enhancing the maturation rate of naive T cells. 66,73 Such rapid turnover of T cells could have detrimental effects on antitumor responses.…”

Section: Immune Effector Cells In the Circulation Of Patients With Camentioning

confidence: 93%

“…The level of spontaneous apoptosis discriminates between patients with cancer and healthy control subjects but not between patients with active disease versus those who are NED after oncologic therapies. 67 However, expression of CCR7, which is also a differentiation marker for T cells, by CD8 + T cells was observed to protect the CD8 + effector cells from apoptosis because CCR7 signaling correlated with higher Bcl-2 expression but lower Bax and Fas expression and phosphoinositide 3-kinase pathway activation in CD8 + T cells. 68 The frequency of circulating CD8 + CCR7 + T cells now emerges as an immune biomarker that might be predictive of survival benefits in patients with cancer.…”

Section: Immune Effector Cells In the Circulation Of Patients With Camentioning

confidence: 97%

“…65 As indicated in Table III, [66][67][68] T cells that undergo spontaneous apoptosis in the circulation of these patients are CD3 + CD95 + , bind Anx, and have increased levels of caspase-3 activity and decreased expression of the TCR-associated ζ chain. 63,69,70 Circulating CD8 + T cells, especially the effector subpopulations (CD8 + CD45RO + CCR7 − CD27 − and CD8 + CD28 − ), have a significantly greater propensity to undergo spontaneous apoptosis than CD4 + T cells in patients with cancer.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…65 The proportion of CD8 + CD95 + T cells that bind Annexin V (Anx) and yet are 7-amino-actinomycin D negative (7AAD − ) or propidium iodide (PI) negative is significantly greater in the peripheral circulation of patients with cancer, including those with head and neck, breast, and ovarian carcinomas and melanoma, than in age-or sex-matched healthy donors. 65 As indicated in Table III, [66][67][68] T cells that undergo spontaneous apoptosis in the circulation of these patients are CD3 + CD95 + , bind Anx, and have increased levels of caspase-3 activity and decreased expression of the TCR-associated ζ chain. 63,69,70 Circulating CD8 + T cells, especially the effector subpopulations (CD8 + CD45RO + CCR7 − CD27 − and CD8 + CD28 − ), have a significantly greater propensity to undergo spontaneous apoptosis than CD4 + T cells in patients with cancer.…”

Section: Immune Effector Cells In the Circulation Of Patients With Camentioning

confidence: 99%

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22. Immune responses to malignancies

Whiteside

2003

Journal of Allergy and Clinical Immunology

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Immune responses to tumor-associated antigens (TAs) are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent the development of metastases. Patients with cancer generate robust immune responses to infectious agents (bacteria and viruses) perceived as a "danger signal" but only ineffective weak responses to TAs, which are considered as "self." This fundamental difference in responses to self versus nonself is further magnified by the ability of tumors to subvert the host immune system. Tumors induce dysfunction and apoptosis in CD8 + antitumor effector cells and promote expansion of regulatory T cells, myeloid-derived suppressor cells, or both, which downregulate antitumor immunity, allowing tumors to escape from the host immune system. The tumor escape is mediated by several distinct molecular mechanisms. Recent insights into these mechanisms encourage expectations that a more effective control of tumorinduced immune dysfunction will be developed in the near future. Novel strategies for immunotherapy of cancer are aimed at the protection and survival of antitumor effector cells and also of central memory T cells in the tumor microenvironment. KeywordsCancer; immunity; tumor escape; immune suppression; effector T cells Evidence accumulated over the last few years convincingly shows that the host immune system is involved in cancer development and progression, as well as control of metastasis. The presence of antitumor cellular responses, humoral responses, or both to tumorassociated antigens (TAs) has been observed in many, but not all, patients with cancer. 1,2 The evidence for such pre-existing antitumor immunity in patients with cancer confirms that the tumor-bearing host is capable of mounting an immune response to TAs. Tumor progression from a single transformed cell to a mass of malignant cells is a multistep process involving a series of genetic changes occurring in human subjects over a period of months or years and culminating in the established tumor. 3 During this period, neither the host immune system nor the developing tumor are idle: those newly emerging tumor cells that are recognized by the immune system are eliminated only to be replaced by genetic tumor variants resistant to immune intervention and giving rise to a heterogenous population of malignant cells found in any tumor. Tumors are genetically unstable, and the emergence of new genetic variants, which is responsible for the tumor heterogeneity, ensures that the tumor survives in the face of the host immune system. Only the tumor cells that manage to avoid recognition escape and survive, whereas those that are recognized by the immune system are eliminated as soon as they arise. The tumor development involves a prolonged NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript series of checks and balances between the host attempting to curtail tumor growth and the tumor benefiting from genetic changes, altering its microenvironment and avoiding immune elimination. Thus the...

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Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck

et al. 2006

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Expression of Pro- and Antiapoptotic Proteins in Circulating CD8+ T Cells of Patients with Squamous Cell Carcinoma of the Head and Neck

Cited by 43 publications

References 22 publications

Tumor-Driven Evolution of Immunosuppressive Networks during Malignant Progression

Tumor-Driven Evolution of Immunosuppressive Networks during Malignant Progression

22. Immune responses to malignancies

Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck

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