Cell Responses In Patients Research Articles

Vaccination of B-CLL Patients with Autologous Dendritic Cells Results in Immunological and Clinical Responses.

B-cell chronic lymphocytic leukemia (B-CLL) is a very attractive disease to be targeted by immunotherapy due to its rather low progression and due to the availability of cancer cells in the peripheral blood. Dendritic cells (DCs) are the most professional antigen presenting cells, but are deficient in B-CLL. Therefore administration of ex vivo generated DCs might improve the anti-leukemic T cell response in patients with B-CLL. Our group reported the first clinical trial with allogeneic DCs stimulated with leukemic cells lysates in B-CLL patients. To answer the question whether autologous DCs might cause a similar immunotherapeutical effect we conducted the present study assessing the safety and feasibility as well as the clinical and immunological responses to autologous monocyte-derived DC immunotherapy in B-CLL patients. Precursor cells for DC generation were obtained using two methods: by plastic adherence of PBMC from leukapheresis or CD14 positive separation through magnetic beads of PBMC from 150mL of peripheral blood. Twelve patients at clinical stage 0 and 2 according to Rai were vaccinated intradermally up to eight times with a mean number of 7.4×106 DCs pulsed with B-CLL cell lysates. Specific CD8+ T cell responses to RHAMM and fibromodulin - recently described as tumor specific antigens (TAA) in B-CLL were evaluated by multi-parametric tetramer-based flow cytometry and ELISPOT assays. Furthermore, the percentage of CD4+CD25hiFoxP3+ T regulatory cells in the peripheral blood over the time of vaccination was assessed. We observed a decrease of peripheral blood leukocytes and B CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. The best clinical response was observed in the patients treated with DCs generated from adherent fraction of PBMC obtained by leukapheresis. No severe toxicities were noted. After the end of therapy the in vitro proliferation of autologous T cells stimulated by DC pulsed with lysates, as well as by lysates alone increased significantly comparing to the values before treatment (1391±2170, p<0.001; 3280±4842, p<0.001). A significant increase of specific cytotoxic CD8+ T lymphocytes against leukemia-associated antigens (RHAMM/CD168 and fibromodulin), was detected after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels (12±9 pg/ml vs. 6±7 pg/ml; p=0.02,) was noted. In patients with the most favorable clinical response we observed a substantial decrease of CD4+/CD25+ cells (14.3±11.3% vs. 28.6±12.5%) and an increase of CD8+/CD25+ cells percentage after DC therapy (49.3±55.7% vs. 8.9±1.9%), as well as a decrease of the frequency of CD4+CD25hiFOXP3+ T regulatory cells. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.

CD4+CD25hi regulatory T‐cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia

CD4(+)CD25(hi)CTLA4(+)FoxP3(+) regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T-cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre-malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL-2 producing T-helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV-persistence-associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia.

Microbiological and Immunological Features of Oral Candidiasis

Candida albicans(C. albicans) is the major infectious agent of oral candidiasis, and both innate immunity and cell-mediated immune response participate in the control of the fungal infections. The aim of this study was to correlate the clinical forms of oral candidiasis with the number of colony forming units (CFU) of C. albicans in saliva and to characterize T cell response in patients with oral candidiasis. Participants included 75 subjects: 36 with lesions of candidiasis and 39 without lesions of oral candidiasis. A 2-ml sample of saliva was collected from all subjects for microbiological analysis. Cytokine levels were determined by ELISA in supernatants of peripheral blood mononuclear cells of 25 patients with oral candidiasis, after in vitro stimulation with C. albicans antigens. In 48% of patients, no association was observed with denture use. C. albicans was detected in the saliva of 91.7% of patients with oral candidiasis, and there was an association between the number of CFU and the presence of oral lesions. A type Th1 immune response was observed in supernatants of peripheral blood mononuclear cells stimulated with C. albicans antigens. In contrast, IL-5 and IL-10 levels were very low or undetectable. Together, this study shows an association between clinical forms of oral candidiasis and the number of colonies of C. albicans in saliva, and that a systemic immune response characterized by the production of TNF-alpha and IFN-gamma is observed in patients with oral candidiasis.

P53‐specific T cell responses in patients with malignant and benign ovarian tumors: Implications for p53 based immunotherapy

Despite intensive treatment, 70% of the ovarian cancer patients will develop recurrent disease, emphasizing the need for new approaches such as immunotherapy. A promising antigenic target for immunotherapy in ovarian cancer is the frequently overexpressed p53 protein. The aim of the study was to evaluate the nature and magnitude of the baseline anti-p53 immune response in ovarian cancer patients. P53-specific T cell responses were detected in both half of the ovarian cancer patients as in the group of control subjects, consisting of women with benign ovarian tumors and healthy controls. Importantly, while in the control group p53-specific immunity was detected among the CD45RA(+) naïve subset of T cells only, the p53-specific T-cell responses in ovarian cancer patients were also present in the CD45RO(+) memory T-cell subset, suggesting that in the cancer patients sufficient amounts of cancer-derived p53 was presented to induce the formation of a p53-specific memory T-cell response. Further characterization of the p53-specific memory T-cell responses revealed that in addition to the type 1 cytokine IFN-gamma also the type 2 cytokines IL-4 and IL-5, as well as the immunosuppressive cytokine IL-10 were produced. Notably, p53-specific T cells were not only detected in the peripheral blood, but also among tumor infiltrating lymphocytes and in tumor-draining lymph nodes. In conclusion, the existence of a weak mixed T-helper type 1 and 2 p53-specific T-cell repertoire supports the rationale of using p53 long peptides in vaccination strategies aiming at the induction of p53-specific Th1/CTL immunity.

CD4+T Cell Responses in Patients with Chronic Hepatitis C Undergoing Peginterferon/Ribavirin Therapy Correlate with Faster, but Not Sustained, Viral Clearance

T cell immune responses may be important for the elimination of chronic hepatitis C virus (HCV) infection during antiviral treatment. In the present study, the kinetics of T cell responses to HCV antigens (NS3-4 and core) were prospectively assessed and were correlated with virologic outcome in 31 patients with chronic HCV infection undergoing peginterferon- alpha 2a/ribavirin therapy. NS3-4--directed T helper cell type 1 (Th1) responses were detected in 77% of patients with a significant decline in viremia at treatment week 4 but were not detected not in those with a slower viral decline. The detectability of NS3-4--directed Th1 responses was associated with faster viremia clearance, was short-lived, and did not seem to be associated with the final treatment outcome.

Regulatory T Cell Abnormalities Associated with Aberrant CD4+ T Cell Responses in Patients with Immune Reconstitution Disease (IRD)

Regulatory T Cell Abnormalities Associated with Aberrant CD4+ T Cell Responses in Patients with Immune Reconstitution Disease (IRD)

CD4+CD25+FOXP3+ Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

BackgroundA wealth of evidence obtained using mouse models indicates that CD4+CD25+FOXP3+ regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4+ T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients.Methodology and Principal FindingsTreg were identified and characterized as CD4+CD25+FOXP3+ using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4+ T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group.Conclusions/SignificanceCollectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.

Allergen‐specific helper T cell response in patients with cow's milk allergy: simultaneous analysis of proliferation and cytokine production by carboxyfluorescein succinimidyl ester dilution assay

The role of antigen-specific T cells in the allergic reaction to cow's milk or in tolerance induction is not yet fully understood. This study was designed to analyse both cow's milk protein (CMP)-specific T cell proliferation and cytokine production simultaneously in children with cow's milk allergy (CMA) in comparison with subjects with various allergic backgrounds. Carboxyfluorescein succinimidyl ester was used to detect cow's milk-specific T cells by flow cytometry. The intra-cytoplasmic cytokine production of these antigen-specific T cells was also analysed. Significant differences of both CMP-specific CD4+ cell proliferation and cytokine production between CMA and non-allergic children were observed. While the proliferative responses of children who recently outgrew CMA were not significantly different from those of patients, the patterns of cytokine production were similar to those of non-allergic children. These results suggest that the presence of CMP-specific T cell clones per se does not produce CMA, but that the T-helper type 2-skewed pattern of those T cells is associated with adverse reactions. Although it is not possible to distinguish between individual patients with and without CMA on the basis of CFSE assays, these results contribute to the understanding of the pathogenesis and tolerance induction of CMA.

Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb ticilimumab

8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical immunologic response to ticilimumab was evidenced by immune-related toxicity (G3 diarrhea in 2 pts, G2 hypophysitis in 1 pt, G3 hepatitis in 2 pts) and by anti-tumor activity: CR in 1 pt (15+ mo), PR in 2 pts (9+, 8 mo), and SD in 3 pts (11, 8+ and 4 mo); the rest had PD at 4 mo or less. A mean of 2 baseline and 7 follow up (range 5–9) time points were tested by tetramer and ELISPOT assays. 4 pts had an increase in MART-1-specific T cells beyond the RCV on 1 or more occasions, but no pt had a consistent pattern of change over time. Indeed, there was no consistent pattern of change in any pt in circulating T cells specific for MART-1, gp100, tyrosinase, EBV, or CMV by tetramer or by ELISPOT assay. One pt had accessible regressing lesions which on biopsy showed heavy infiltration by CD8+/Granzyme B+ CTL and a 10-fold enrichment of gp100-specific T cells compared to his peripheral blood. Conclusion: Ticilimumab administered monthly induces immune-related phenomena and tumor responses in patients with melanoma without a demonstrable expansion of circulating melanoma antigen-specific T cells. Evaluation of melanoma antigen-specific T cells within the tumor may be a better way to study the mechanism of antitumor activity of CTLA4 blocking mAb. [Table: see text]

Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests

BackgroundDendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients. Patients and methodsWe evaluated the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. CEA-specific T cell reactivity was monitored in peripheral blood, biopsies of vaccination sites and post-treatment DTH skin tests, and when available also in resected abdominal lymph nodes and tumor tissue. ResultsTen patients were vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. High numbers of CEA-specific T cells were detected in post-treatment DTH biopsies in seven out of 10 patients, which produced high amounts of interferon (IFN)-γ upon stimulation with CEA-loaded target cells. These responses were not found in biopsies of first vaccination sites, indicating a de novo T cell induction or at least a strong potentiation by the vaccine. In addition, CEA-specific T cells were detected in a resected lymph node in one patient, but not in peripheral blood or tumor tissue. ConclusionsVaccination with CEA-peptide loaded mature DCs induced potent CEA-specific T cell responses in advanced colorectal cancer patients. In this study, antigen-specific T cell responses were readily detected in DTH skin tests, much less in abdominal lymph nodes, and not in peripheral blood and tumor tissue.

Snapshots for May 2006

Snapshots for May 2006

421 Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cell responses in patients with chronic hepatitis C treated with pegylated interferon plus ribavirin

421 Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cell responses in patients with chronic hepatitis C treated with pegylated interferon plus ribavirin

Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts

Vaccination with dendritic cells (DCs) as professional antigen presenting cells generated from autologous leukemic blasts might elicit anti-leukemic T cell responses in patients with acute myeloid leukemia (AML). To test this hypothesis, autologous AML-DC were generated under good manufacturing practice (GMP) conditions and injected s.c. into five AML patients up to four times at a biweekly interval. No severe adverse side effects were observed. Three patients remained in a stable condition for 5.5-13 months and two patients died from rapidly progressive AML. Compared to the initial T cell frequency, enzyme linked immunosorbent spot (ELISPOT) assays revealed a significant increase of granzyme B releasing CD8+ T cells specifically recognizing the PRAME derived peptide (ALYVDSLFFL), a leukemia associated antigen expressed by AML blasts. The cytokine levels in the serum of vaccination AML patients as assessed by cytokine bead assay changed over the period of vaccination to an elevated type 1 T helper cell pattern. Interferon gamma production by CD4+ T helper cells increased during vaccination. In summary, we demonstrated that autologous AML-DC vaccination is well tolerated and can result in an enhanced and specific response of cytotoxic T cells in AML patients.

P.184 CD4+, CD8+ and CD16+ T cell responses in patients with chronic HCV associated with herpes virus infection

P.184 CD4+, CD8+ and CD16+ T cell responses in patients with chronic HCV associated with herpes virus infection

P.284 Neurocognitive alterations in patients with HCV infection with and without abnormal transaminases

Background/Aims: To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-α therapy, 11 untreated anti-HCV positive individuals and 10 healthy controls.Methods: Proliferative T helper cell responses to recombinant HCV core and non-structural antigens were monitored by 3H-thymidine uptake assay and compared to quantitative viraemia levels and HCV genotypes.Results: Of the 30 treated patients, six had sustained complete responses (20%), another six were transient therapy responders (20%) and 18 were non-responders (60%). Viral clearance was associated with the HCV genotype 3 and low pretreatment viral load. In a substantial proportion and complete and transient therapy responders, increased NS3-, helicase- and NS4-antigen-specific T cell responses were observed during interferon-α therapy. In non-responders and in the later clinical courses of transient therapy responders, core and NS5-specific T cell responses dominated. In addition, 11 untreated anti-HCV antibody positive individuals were studied. Two HCV-RNA negative patients who might have recovered from HCV infection showed strong persistent lymphoproliferative responses to NS3, helicase and NS4 antigens, whereas seven of the nine viraemic patients reacted with HCV core or NS5 antigens.Conclusions: Interferon-α treatment enhances NS3-, helicase- and NS4-antigen-specific T helper cell responses in patients with viral clearance, whereas viral persistence was associated with increased T cell reactivities against core and NS5 antigens. Immunogenetical, immunological and virological factors that may influence differential T cell induction in chronic hepatitis C are discussed.

HIV infection in older patients in the HAART era

An increasing number of patients over 50 years of age are now living with HIV, owing to highly active antiretroviral therapy (HAART) that prolongs survival on the one hand and to late diagnosis of patients living with occult HIV infection on the other hand. Most studies have shown that compared with younger patients, patients over 50 generally have a slower immunological response to HAART and experience more rapid clinical progression, despite a better virological response. Low thymic output probably plays a role in the poorer CD4 cell response in patients initiating HAART over 50 years. Management of HIV infection in older patients is particularly complex, mainly because they are more likely to have co-morbidities necessitating specific medications that may interact with antiretroviral drugs. More controlled studies of HAART efficacy and tolerability in such patients are needed to establish specific management guidelines. Information campaigns targeting older patients and their doctors are also needed to ensure timely diagnosis of HIV infection and antiretroviral treatment initiation.

In HIV Type 1-Infected Children Cytotoxic T Lymphocyte Responses Are Associated with Greater Reduction of Viremia under Antiretroviral Therapy

The evolution of the HIV-specific CD8+ T cell response in patients receiving potent combination therapy has been well documented in adult patients. However, no study reported whether baseline HIV-specific CD8+ T cell response is linked to treatment outcome. The aims of this study were to investigate both the impact of baseline memory cytotoxic T lymphocytes (CTL) on treatment outcome and the effect of potent therapy on memory HIV-specific CTL in HIV-1-infected pediatric patients. The study group comprised 30 children who started a first-line combination treatment including at least three drugs from two different classes and were longitudinally followed during treatment. Their memory HIV-specific responses were measured at baseline and during treatment, as well as their plasma viremia and CD4+ levels. The intensity of memory Gag-specific CTL and the breadth of the CTL response at the beginning of treatment were significantly correlated with lower plasma viral load during treatment, independently of baseline plasma viral load, CD4+ counts, and age. Children with partially controlled viral replication had enhanced Gag-specific CTL compared to their baseline value. This improvement of antiviral responses during treatment was not observed when viral replication was either fully suppressed or uncontrolled. In conclusion, our results show that higher baseline HIV-specific CTL are linked to lower viremia under combination therapy. This result adds further support to the hypothesis that cooperation between the antiviral immune response and antiviral drugs could be helpful for therapeutic management of HIV-infected patients.

No Indication for a Defect in Toll-Like Receptor Signaling in Patients with Hyper-IgE Syndrome

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.

The study of inhibitory peptides on T cell activation in rheumatoid arthritis

To study the inhibitory role of altered HA308 - 317 peptides in T cell responses in patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DRB1 positive RA patients. T cell responses to altered HA308-317 peptides were examined by using (3)H incorporation assay. The level of IL-2 and IFNgamma in the supernatants was identified by an enzyme-linked immunosorbent assay. The CD69 expression on T cell surface was studied by using flow cytometry. Compared to wild type CII263 - 272 or HA308 - 317, altered HA308 - 317 peptides failed to stimulate T cell proliferation (P < 0.05) and production of IL-2 as well as IFNgamma and resulted in lower expression of CD69 in RA patients (P < 0.05). SI values for T cell coincubated with altered HA308 - 317 peptides and CII263 - 272 or wild type HA308 - 317 were significantly lower than coincubated with CII263 - 272 and wild type HA308 - 317 alone (P < 0.05). Substitution of TCR-binding residue of HA308 - 317 yielded weak or non-T-cell stimulating peptides, which might be potentially effective in blocking abnormal T cell responses in RA.

A local enrichment of regulatory T cells within the tumor tissue might suppress an effective anti-tumor T cell response in patients with head and neck cancer

9666 Background: Head and neck cancer has traditionally been regarded as a tumor type exerting a suppressive effect on the T cell-mediated immune system. Here, we examined the expression of a variety of tumor-associated antigens as possible targets for a T cell response in tumors of patients with head-and-neck cancer. Next, we analyzed whether a local accumulation of regulatory T cells within the tumor might contribute to a suppression of an effective immune response. Methods: We analyzed the expression of cancer testis (CT) antigens NY-ESO-1, MAGE-A3, MAGE-C1, MAGE-E1, SSX-1, SSX-2, ADAM2 (CT15), LIP1 (CT17), and HOM-TES-85 in tumor samples and adjacent healthy tissue of patients with head and neck cancer (N=35) using rt-PCR. Furthermore, we analyzed the expression of Foxp3, a marker gene for regulatory T cells (Treg), in tissue samples of the same patients using real-time PCR. For comparison, quantitative PCR for Foxp3 expression was also applied to non-malignant tissue derived from inflamed tonsils of patients who had undergone tonsillectomy (N=11). Results: We observed expression of a variety of CT antigens in tumor tissue derived from patients with head and neck cancer. MAGE-A3 was expressed in 60%, SSX-1 in 37%, MAGE-C1 in 17%, MAGE-E1 in 14%, and SSX-2 in 11% of cases. CT antigens less frequently expressed were HOM-TES-85 in 9%, NY-ESO-1 in 6%, and CT17 in 3% of cases. CT15 was not expressed in any of the tumor samples. None of the healthy tissue samples adjacent to the tumor expressed any CT antigens. Real-time PCR revealed a higher expression of Foxp3 within tumor tissue than within adjacent healthy tissue (p<0.05). Importantly, expression of Foxp3 was not increased in tissue derived from inflamed tonsils, pointing to a specific homing of regulatory T cells into the tumor. Conclusions: Tumors of patients with head and neck cancer express a variety of CT antigens which might serve as targets for a T cell-mediated anti-tumor response. However, a local enrichment of regulatory T cells expressing Foxp3 might contribute to the suppression of such a T cell response. We are currently investigating which local factors lead to an enrichment of regulatory T cells within the tumor. No significant financial relationships to disclose.