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Background: For head and neck squamous cell cancer (HNSCC), standard therapy consists of surgery, radiation, and/or chemotherapy. Antineoplastic immunotherapy could be an option in an adjuvant setting and is already in palliation. A functional immune system is a prerequisite for successful immunotherapy. However, effects of the standard-of-care therapy on the patients' immune system are not fully understood.Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients with HNSCC (n = 37) and healthy controls (n = 10). PBMC were stimulated with staphylococcal enterotoxin B (SEB). Simultaneous expression of various cytokines was measured in CD4+ and CD8+ T cells by multicolor flow cytometry, and polyfunctional cytokine expression profiles were determined on a single-cell basis.Results: Expression levels of all measured cytokines in CD4+ T cells were higher in patients after chemoradiotherapy (CRT) as compared to untreated HNSCC patients or normal controls. After CRT, the frequency of polyfunctional CD4+ T cells, which simultaneously expressed multiple cytokines, was significantly increased as compared to untreated patients (p < 0.01).Conclusion: CRT increases polyfunctionality of CD4+ T cells in HNSCC patients, suggesting that standard-of-care therapy can promote immune activity in immune cells. These polyfunctional CD4+ T cells in the blood of treated HNSCC patients are expected to be responsive to subsequent immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

The immunosuppressive drug Rapamycin (RAPA) has been shown to promote expansion of CD4+IL-10+ natural human regulatory T cells (nTreg) in vitro and in vivo. RAPA effects on inducible Treg (Tri) are unknown, and this study explores in vitro responses of Tri to this drug. CD4+CD25neg T cells isolated from PBMC of normal donors were used to generate Tri cells. Expanded Tri cells were tested for surface markers, expression of survival proteins, resistance to apoptosis and the ability to suppress proliferation of autologous CD4+CD25neg responder T cells (RC) in functional assays. RAPA was found to promote the generation of human Tri cells from autologous CD4+CD25neg precursors in peripheral blood. Tri cells + RAPA mediated higher suppression (p<0.01) of RC proliferation than Tri cells cultured without RAPA. Tri cells + RAPA also expressed higher levels of FasL and granzyme B (p<0.002), produced more IL-IO and TGF-ßl and were more resistant to activation-induced cell death (p<0.02). RAPA up-regulated expression of the Bcl-2 family anti-apoptotic proteins in Tri. In addition, stimulation of Tri by LPS + RAPA resulted in increased proliferation and resistance to apoptosis. RAPA favors in vitro generation of inducible human Treg (Tri) from CD4+CD25neg precursor cells and significantly enhances their survival and suppressor functions. [ABSTRACT FROM AUTHOR]

The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs) while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy. [ABSTRACT FROM AUTHOR]

In a well-established murine abortion model, stress is thought to trigger fetal rejection by inducing a proinflammatory immune response via substance P (SP), being tumour necrosis factor (TNF)-α-producing CD8+ T cells involved. Interestingly, the SP metabolite SP5-11 also binds to SP receptors and mediates SP-like effects on immune cells at sites of inflammation. No data were available regarding the effects of SP5-11 on pregnancy outcome in the CBA/J × DBA/2J abortion-prone combination. We investigated the influence of SP5-11 in contrast to stress or SP on the abortion rate and the cytokine production by lymphocytes as well as on the levels of CD8+ T cells. Stress and SP boosted the abortion rate and increased the percentage of type 1 [TNF-α, interferon-γ, interleukin (IL)-12] and type 2 (IL-4 and IL-10) cytokine-producing lymphocytes in blood and decidua, predominantly CD8+ T cells. Interestingly, SP5-11 did not significantly affect the abortion rate or cytokine production in the decidua, while increasing the Th1 and Th2 cytokine production systemically. Our data suggest that stress and SP induce abortion by augmenting the local levels of TNF-α, which seems therefore to be a potent trigger of miscarriage. On the contrary, the SP metabolite SP5-11 only affects the systemic cytokine production without boosting the abortion rate in this experimental model. [ABSTRACT FROM AUTHOR]

In recent years, natural killer (NK) cells, as well as subpopulations of T cells, have been found to express diverse NK receptors (NKRs) for HLA class I molecules. We have characterized NKR phenotypes in lymphoproliferative disorders of NK or T-cell type. Peripheral blood of patients with lymphoproliferative disorders (n = 9) was analysed by multiparametric immunofluorescence flow cytometry with eight different antibodies against NKRs. Abnormal neoplastic cell populations from different types of NK or T-cell lymphoproliferative disorders lacked diversity in their NKR repertoires, i.e. all or none of the abnormal cells expressed individual NKRs and this expression occurred at single levels of intensity. This pattern of expression was specific for lymphoproliferative disorders as these resticted NKR repertoires were not found either in healthy donors (n = 9) or in patients with viral or autoimmune disease (n = 5). We conclude that NKRs are clonally expressed in lymphoproliferative disorders of NK or T-cell origin. NKR repertoires may represent a novel tool in diagnosing clonal disorders of NK and T-cell type. [ABSTRACT FROM AUTHOR]